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MeSH Review


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Disease relevance of Forelimb

  • Okihiro syndrome (OS) is defined by forelimb defects associated with the eye disorder Duane anomaly and results from mutations in the gene SALL4 [1].
  • Direct evidence for a role of Tbx5 in forelimb development was provided by the discovery that mutations in human TBX5 cause Holt-Oram Syndrome (HOS), a dominant disorder characterised predominantly by upper(fore) limb defects and heart abnormalities [2].
  • By contrast, the synaptophysin demonstrated no statistically significant changes in expression at 3 or 7 days but demonstrated statistically significant increases at 14, 30, and 60 days in the forelimb, hindlimb, and parietal neocortical regions ipsilateral to the infarction as well as increased distribution in the contralateral parietal neocortex [3].
  • Convulsions typically affected by these manipulations were PTZ-induced myoclonic jerk and face and forelimb clonus and kainic acid-induced convulsions [4].
  • Moreover, the local intra-arterial infusion of bradykinin into forelimbs perfused at constant inflow fails to increase skin lymph protein concentration after 60 minutes of systemic hypotension [5].

Psychiatry related information on Forelimb


High impact information on Forelimb

  • Tbx5 and Sall4 interact both positively and negatively to finely regulate patterning and morphogenesis of the anterior forelimb and heart [11].
  • Here we show that Tbx5 regulates Sall4 expression in the developing mouse forelimb and heart; mice heterozygous for a gene trap allele of Sall4 show limb and heart defects that model human disease [11].
  • Heterozygous Tbx5(del/+) mice were generated to study the mechanisms by which TBX5 haploinsufficiency causes cardiac and forelimb abnormalities seen in Holt-Oram syndrome [12].
  • Here we report that conditional disruption of Fgf8 in the forelimb of developing mice bypasses embryonic lethality and reveals a requirement for Fgf8 in the formation of the stylopod, anterior zeugopod and autopod [13].
  • Inactivation of Lbx1h, which is specifically expressed in migrating muscle precursor cells, led to a lack of extensor muscles in forelimbs and an absence of muscles in hindlimbs [14].

Chemical compound and disease context of Forelimb


Biological context of Forelimb


Anatomical context of Forelimb

  • We conclude that Tbx5 is not essential for the early establishment of the limb field in the lateral plate mesoderm but is a primary and direct initiator of forelimb bud formation [24].
  • The quantitative 14C-deoxyglucose (DG) autoradiographic technique has been used to study changes in cerebral metabolism during forelimb movements induced by graded stimulation of motor cortex [25].
  • In order to see whether Msx1 is expressed in this migrating population, we have grafted somites from the forelimb level of Msx1(nlacZ )mouse embryos into a chick host embryo [23].
  • Animals defective for hoxd-12 are viable, fertile, and appear outwardly normal yet have minor autopodal defects in the forelimb which include a reduction in the bone length of metacarpals and phalanges, and a malformation of the distal carpal bone d4 [26].
  • Spontanteous mutations in the T-box gene TBX3, result in the human ulnar-mammary syndrome, a dominant developmental disorder characterized by abnormal forelimb and apocrine gland development [27].

Associations of Forelimb with chemical compounds

  • Rather, the unique structure of the forelimb is probably the result of evolved changes in the short head of biceps brachii to enhance its role as a forearm flexor [28].
  • To determine whether defective muscle metabolism is restricted to the region of injury, we studied protein and glucose metabolism in forelimb muscles of rats 48 h after a scalding injury of their hindquarters [29].
  • Exogenous thyroid hormone (TH) induces premature differentiation of the zebrafish pectoral fins, which are analogous to the forelimbs of tetrapods [30].
  • Effects of intravenously infused histamine on canine forelimb transvascular protein efflux following adrenergic receptor blockade [31].
  • Infusion of enprofylline at 5 mg/min decreased forelimb arterial pressures and systemic pressure [22].

Gene context of Forelimb

  • We hypothesize that Pitx1 serves to critically modulate morphogenesis, growth, and potential patterning of a specific hindlimb region, serving as a component of the morphological and growth distinctions in forelimb and hindlimb identity [32].
  • Tbx5 is essential for forelimb bud initiation following patterning of the limb field in the mouse embryo [24].
  • In this study, we show that malformation of the forelimb zeugopod in Hoxa11/Hoxd11 double mutants is a consequence of interruption at multiple steps during the formation of the radius and ulna [33].
  • Mice lacking Lbx1 exhibit an extensive loss of limb muscles, although some forelimb and hindlimb muscles are still present [34].
  • As a result, genes such as Bmp2 or Hoxd genes are expressed symmetrically along the AP axis of the forelimb buds, and/or later, of the autopod [35].

Analytical, diagnostic and therapeutic context of Forelimb

  • To further assess the potential anti-inflammatory effects of enprofylline, we infused it intra-arterially into the canine forelimb before and during a local intra-arterial infusion of histamine (4 micrograms/min) while monitoring forelimb skin lymph parameters [22].
  • Electrolytic destruction of the SI lower-jaw representation in four additional control rats with neonatal forelimb amputation did not significantly reduce the percentage of hindlimb-responsive sites in the SI stump field during GABA-receptor blockade (P = 0.98) [36].
  • 1. In anesthetized, immobilized cats, individual axonal responses to movement of forelimb G hairs were recorded in the ipsilateral cuneate fasciculus at C1-C2 with a glass-insulated tungsten microelectrode [37].
  • Intraperitoneal injection of ethanol (1-2 g/kg) and chlordiazepoxide (2-16 mg/kg) suppressed susceptibility to audiogenically induced, clonic-tonic seizures and antagonized forelimb tremor in rats undergoing ethanol withdrawal, 30 min after treatment [38].
  • Supraorbital, posteroorbital, lateral cervical, median cervical, submental, and carpal forelimb F-SCs were cut on a cryostat and were either prepared for anti-human protein gene product (PGP 9.5) immunofluorescence or stained using the Winkelmann silver technique [39].


  1. sall4 acts downstream of tbx5 and is required for pectoral fin outgrowth. Harvey, S.A., Logan, M.P. Development (2006) [Pubmed]
  2. Tbx5 is required for forelimb bud formation and continued outgrowth. Rallis, C., Bruneau, B.G., Del Buono, J., Seidman, C.E., Seidman, J.G., Nissim, S., Tabin, C.J., Logan, M.P. Development (2003) [Pubmed]
  3. Enhanced neocortical neural sprouting, synaptogenesis, and behavioral recovery with D-amphetamine therapy after neocortical infarction in rats. Stroemer, R.P., Kent, T.A., Hulsebosch, C.E. Stroke (1998) [Pubmed]
  4. Mineralocorticoid receptors mediate the enhancing effects of corticosterone on convulsion susceptibility in mice. Roberts, A.J., Keith, L.D. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  5. Effects of locally and systemically infused bradykinin on transvascular fluid and protein transfer in the canine forelimb. Maciejko, J.J., Marciniak, D.L., Gersabeck, E.F., Grega, G.J. J. Pharmacol. Exp. Ther. (1978) [Pubmed]
  6. beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Zheng, H., Jiang, M., Trumbauer, M.E., Sirinathsinghji, D.J., Hopkins, R., Smith, D.W., Heavens, R.P., Dawson, G.R., Boyce, S., Conner, M.W., Stevens, K.A., Slunt, H.H., Sisoda, S.S., Chen, H.Y., Van der Ploeg, L.H. Cell (1995) [Pubmed]
  7. Electroshock- and pentylenetetrazol-induced seizures in genetically epilepsy-prone rats (GEPRs): differences in threshold and pattern. Browning, R.A., Wang, C., Lanker, M.L., Jobe, P.C. Epilepsy Res. (1990) [Pubmed]
  8. Activity of ventrolateral thalamic neurons in relation to a simple reaction time task in the cat. Schmied, A., Bénita, M., Condé, H., Dormont, J.F. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (1979) [Pubmed]
  9. The analgesic effects of administering fentanyl or medetomidine in the lumbosacral epidural space of cats. Duke, T., Cox, A.M., Remedios, A.M., Cribb, P.H. Veterinary surgery : VS : the official journal of the American College of Veterinary Surgeons. (1994) [Pubmed]
  10. Differential effects of GDNF treatment on rotational asymmetry, skilled forelimb use deficits and sensory neglect in unilateral 6-OHDA-lesioned rats. Schneider, J.S., Peacock, V. Restorative neurology and neuroscience. (1998) [Pubmed]
  11. Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart. Koshiba-Takeuchi, K., Takeuchi, J.K., Arruda, E.P., Kathiriya, I.S., Mo, R., Hui, C.C., Srivastava, D., Bruneau, B.G. Nat. Genet. (2006) [Pubmed]
  12. A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease. Bruneau, B.G., Nemer, G., Schmitt, J.P., Charron, F., Robitaille, L., Caron, S., Conner, D.A., Gessler, M., Nemer, M., Seidman, C.E., Seidman, J.G. Cell (2001) [Pubmed]
  13. Fgf8 is required for outgrowth and patterning of the limbs. Moon, A.M., Capecchi, M.R. Nat. Genet. (2000) [Pubmed]
  14. Early specification of limb muscle precursor cells by the homeobox gene Lbx1h. Schäfer, K., Braun, T. Nat. Genet. (1999) [Pubmed]
  15. Non-specific supersensitivity of striatal dopamine receptors after 6-hydroxydopamine lesion of the nigrostriatal pathway. Costall, B., Naylor, R.J., Pycock, C. Eur. J. Pharmacol. (1976) [Pubmed]
  16. Embryonic mesencephalic grafts increase levodopa-induced forelimb hyperkinesia in parkinsonian rats. Steece-Collier, K., Collier, T.J., Danielson, P.D., Kurlan, R., Yurek, D.M., Sladek, J.R. Mov. Disord. (2003) [Pubmed]
  17. Pirenzepine-sensitive component of forelimb vascular resistance and heart rate in cats. Stein, R., Bachoo, M., Polosa, C. J. Auton. Nerv. Syst. (1995) [Pubmed]
  18. Nimodipine treatment to assess a modified mouse model of intracerebral hemorrhage. Ma, B., Zhang, J. Brain Res. (2006) [Pubmed]
  19. Facilitatory effects of 4-aminopyridine on neuromuscular transmission in disease states. Kim, Y.I., Goldner, M.M., Sanders, D.B. Muscle Nerve (1980) [Pubmed]
  20. Development of mouse embryos in vitro: preimplantation to the limb bud stage. Chen, L.T., Hsu, Y.C. Science (1982) [Pubmed]
  21. Interactions among inflammatory mediators on edema formation in the canine forelimb. Amelang, E., Prasad, C.M., Raymond, R.M., Grega, G.J. Circ. Res. (1981) [Pubmed]
  22. Anti-inflammatory actions of enprofylline, a modified xanthine, in the canine forelimb. Dobbins, D.E., Soika, C.Y., Buehn, M.J., Dabney, J.M. Circ. Res. (1989) [Pubmed]
  23. The homeobox gene Msx1 is expressed in a subset of somites, and in muscle progenitor cells migrating into the forelimb. Houzelstein, D., Auda-Boucher, G., Chéraud, Y., Rouaud, T., Blanc, I., Tajbakhsh, S., Buckingham, M.E., Fontaine-Pérus, J., Robert, B. Development (1999) [Pubmed]
  24. Tbx5 is essential for forelimb bud initiation following patterning of the limb field in the mouse embryo. Agarwal, P., Wylie, J.N., Galceran, J., Arkhitko, O., Li, C., Deng, C., Grosschedl, R., Bruneau, B.G. Development (2003) [Pubmed]
  25. Functional metabolic mapping during forelimb movement in rat. I. Stimulation of motor cortex. Collins, R.C., Santori, E.M., Der, T., Toga, A.W., Lothman, E.W. J. Neurosci. (1986) [Pubmed]
  26. A mutational analysis of the 5' HoxD genes: dissection of genetic interactions during limb development in the mouse. Davis, A.P., Capecchi, M.R. Development (1996) [Pubmed]
  27. Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome. Davenport, T.G., Jerome-Majewska, L.A., Papaioannou, V.E. Development (2003) [Pubmed]
  28. Telemetered electromyography of forelimb muscle chains in gibbons (Hylobates lar). Jungers, W.L., Stern, J.T. Science (1980) [Pubmed]
  29. Systemic response to thermal injury in rats. Accelerated protein degradation and altered glucose utilization in muscle. Clark, A.S., Kelly, R.A., Mitch, W.E. J. Clin. Invest. (1984) [Pubmed]
  30. The role of thyroid hormone in zebrafish and axolotl development. Brown, D.D. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  31. Effects of intravenously infused histamine on canine forelimb transvascular protein efflux following adrenergic receptor blockade. Grega, G.J., Marciniak, D.L., Jandhyala, B.S., Raymond, R.M. Circ. Res. (1980) [Pubmed]
  32. Role of the Bicoid-related homeodomain factor Pitx1 in specifying hindlimb morphogenesis and pituitary development. Szeto, D.P., Rodriguez-Esteban, C., Ryan, A.K., O'Connell, S.M., Liu, F., Kioussi, C., Gleiberman, A.S., Izpisúa-Belmonte, J.C., Rosenfeld, M.G. Genes Dev. (1999) [Pubmed]
  33. Multiple roles of Hoxa11 and Hoxd11 in the formation of the mammalian forelimb zeugopod. Boulet, A.M., Capecchi, M.R. Development (2004) [Pubmed]
  34. Lbx1 is required for muscle precursor migration along a lateral pathway into the limb. Gross, M.K., Moran-Rivard, L., Velasquez, T., Nakatsu, M.N., Jagla, K., Goulding, M. Development (2000) [Pubmed]
  35. Embryonic retinoic acid synthesis is required for forelimb growth and anteroposterior patterning in the mouse. Niederreither, K., Vermot, J., Schuhbaur, B., Chambon, P., Dollé, P. Development (2002) [Pubmed]
  36. Source of inappropriate receptive fields in cortical somatotopic maps from rats that sustained neonatal forelimb removal. Lane, R.D., Stojic, R.S., Killackey, H.P., Rhoades, R.W. J. Neurophysiol. (1999) [Pubmed]
  37. Response of forelimb guard hair afferent units to air-jet stimulation of entire receptive field. Goldfinger, M.D., Amassian, V.E. J. Neurophysiol. (1980) [Pubmed]
  38. Differential sensitivity of ethanol withdrawal signs in the rat to gamma-aminobutyric acid (GABA)mimetics: blockade of audiogenic seizures but not forelimb tremors. Frye, G.D., McCown, T.J., Breese, G.R. J. Pharmacol. Exp. Ther. (1983) [Pubmed]
  39. Innervation of nonmystacial vibrissae in the adult rat. Fundin, B.T., Arvidsson, J., Rice, F.L. J. Comp. Neurol. (1995) [Pubmed]
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