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Phox2b  -  paired-like homeobox 2b

Mus musculus

Synonyms: Dilp1, GENA 269, NBPhox, Neuroblastoma Phox, PHOX2B homeodomain protein, ...
 
 
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Disease relevance of Phox2b

  • Constriction of the pupil is a parasympathetic response mediated by the ciliary ganglion and we find that in Phox2b heterozygous mutants it is highly atrophic [1].
  • Haploinsufficiency for Phox2b in mice causes dilated pupils and atrophy of the ciliary ganglion: mechanistic insights into human congenital central hypoventilation syndrome [1].
  • OBJECTIVES: To determine whether newborn mice with heterozygous targeted deletion of the transcription factor Phox2b would display sleep-disordered breathing [2].
 

High impact information on Phox2b

  • A primary function of these proteins is to coordinate the spatial and temporal activation of the homeodomain protein Phox2b, which in turn acts as a binary switch in the selection of motor neuron or serotonergic neuronal fate [3].
  • In addition, as in Phox2b-deficient mice, the development of most (nor)adrenergic centers is compromised in Rnx mutants [4].
  • Whereas the oculomotor and the trochlear neurons require Phox2a for their proper development, the migration of the facial branchiomotor neurons depends on Phox2b [5].
  • Phox2b is necessary for the development of the autonomic nervous system and when absent one of the consequences is that all parasympathetic ganglia fail to form [1].
  • We report here that it is caused by a point mutation that introduces a stop codon close to the start of the coding sequence of the paired-like homeobox transcription factor Phox2b [1].
 

Biological context of Phox2b

 

Anatomical context of Phox2b

 

Associations of Phox2b with chemical compounds

  • Expression of Ret-, p75(NTR)-, Phox2a-, Phox2b-, and tyrosine hydroxylase-immunoreactivity by undifferentiated neural crest-derived cells and different classes of enteric neurons in the embryonic mouse gut [11].
  • Ventilatory response to hyperoxia in newborn mice heterozygous for the transcription factor Phox2b [12].
 

Other interactions of Phox2b

  • The closely related homeobox genes Phox2a and Phox2b are expressed in all central and peripheral noradrenergic neurons [6].
  • Most adrenal medullary cells in Mash1(-/-) mice identified by Phox2b immunoreactivity, lack the catecholaminergic marker tyrosine hydroxylase [13].
  • The expression of Ret-, Phox2a-, Phox2b- and p75(NTR)-immunoreactivity by two classes of enteric neurons that differentiate prior to birth was also examined [11].
  • We conclude that the neural crest cell population that arises from the vagal level of the neural axis and that populates the stomach, midgut, and hindgut expresses Phox2b, Ret, and p75 [10].
  • In the current study, by E12.5 and E14.5, about 25% and 47%, respectively, of Phox2b(+) cells in the small intestine were immunoreactive to the pan-neuronal protein, ubitquitin hydrolase (PGP9.5), and the percentage did not change dramatically from E14.5 onward [14].
 

Analytical, diagnostic and therapeutic context of Phox2b

  • The location and sequence of appearance of enteric neuron precursors deduced from the explants grown under the kidney capsule or in organ culture was very similar to that seen with the Phox2b, Ret, and p75 antisera [10].
  • The use of the electrophoretic mobility shift assay showed that Phox2b/PMX2b is capable of specifically interacting with this site, and cotransfection experiments demonstrated that it is capable of transactivating the human Phox2a promoter [8].

References

  1. Haploinsufficiency for Phox2b in mice causes dilated pupils and atrophy of the ciliary ganglion: mechanistic insights into human congenital central hypoventilation syndrome. Cross, S.H., Morgan, J.E., Pattyn, A., West, K., McKie, L., Hart, A., Thaung, C., Brunet, J.F., Jackson, I.J. Hum. Mol. Genet. (2004) [Pubmed]
  2. Sleep-disordered breathing in newborn mice heterozygous for the transcription factor Phox2b. Durand, E., Dauger, S., Pattyn, A., Gaultier, C., Goridis, C., Gallego, J. Am. J. Respir. Crit. Care Med. (2005) [Pubmed]
  3. Coordinated temporal and spatial control of motor neuron and serotonergic neuron generation from a common pool of CNS progenitors. Pattyn, A., Vallstedt, A., Dias, J.M., Samad, O.A., Krumlauf, R., Rijli, F.M., Brunet, J.F., Ericson, J. Genes Dev. (2003) [Pubmed]
  4. Formation of brainstem (nor)adrenergic centers and first-order relay visceral sensory neurons is dependent on homeodomain protein Rnx/Tlx3. Qian, Y., Fritzsch, B., Shirasawa, S., Chen, C.L., Choi, Y., Ma, Q. Genes Dev. (2001) [Pubmed]
  5. Reciprocal gene replacements reveal unique functions for Phox2 genes during neural differentiation. Coppola, E., Pattyn, A., Guthrie, S.C., Goridis, C., Studer, M. EMBO J. (2005) [Pubmed]
  6. Specification of the central noradrenergic phenotype by the homeobox gene Phox2b. Pattyn, A., Goridis, C., Brunet, J.F. Mol. Cell. Neurosci. (2000) [Pubmed]
  7. The Phox2b transcription factor coordinately regulates neuronal cell cycle exit and identity. Dubreuil, V., Hirsch, M.R., Pattyn, A., Brunet, J.F., Goridis, C. Development (2000) [Pubmed]
  8. Sp proteins and Phox2b regulate the expression of the human Phox2a gene. Flora, A., Lucchetti, H., Benfante, R., Goridis, C., Clementi, F., Fornasari, D. J. Neurosci. (2001) [Pubmed]
  9. Role of Phox2b and Mash1 in the generation of the vestibular efferent nucleus. Tiveron, M.C., Pattyn, A., Hirsch, M.R., Brunet, J.F. Dev. Biol. (2003) [Pubmed]
  10. A single rostrocaudal colonization of the rodent intestine by enteric neuron precursors is revealed by the expression of Phox2b, Ret, and p75 and by explants grown under the kidney capsule or in organ culture. Young, H.M., Hearn, C.J., Ciampoli, D., Southwell, B.R., Brunet, J.F., Newgreen, D.F. Dev. Biol. (1998) [Pubmed]
  11. Expression of Ret-, p75(NTR)-, Phox2a-, Phox2b-, and tyrosine hydroxylase-immunoreactivity by undifferentiated neural crest-derived cells and different classes of enteric neurons in the embryonic mouse gut. Young, H.M., Ciampoli, D., Hsuan, J., Canty, A.J. Dev. Dyn. (1999) [Pubmed]
  12. Ventilatory response to hyperoxia in newborn mice heterozygous for the transcription factor Phox2b. Ramanantsoa, N., Vaubourg, V., Dauger, S., Matrot, B., Vardon, G., Chettouh, Z., Gaultier, C., Goridis, C., Gallego, J. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  13. Development of chromaffin cells depends on MASH1 function. Huber, K., Brühl, B., Guillemot, F., Olson, E.N., Ernsberger, U., Unsicker, K. Development (2002) [Pubmed]
  14. Acquisition of neuronal and glial markers by neural crest-derived cells in the mouse intestine. Young, H.M., Bergner, A.J., Müller, T. J. Comp. Neurol. (2003) [Pubmed]
 
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