Disease relevance of Mid1

• After 18.5 days of development, 96% of Insig-DKO embryos had defects in midline facial development, ranging from cleft palate (52%) to complete cleft face (44%) [1].
• Retraction of radial glial endfeet, midline fusion of brain hemispheres, and gliosis also occurred, similar to type II cobblestone lissencephaly as seen in congenital muscular dystrophy [2].
• Twenty-five percent had exencephaly and 19% had omphalocele (normal frequencies, < 1%), indicating high frequencies of midline defects, particularly in cranial neurulation [3].
• The disease phenotype includes developmental midline malformations, sensory hearing loss, and a delayed-onset generalized dystonia syndrome in monozygotic twins [4].
• T-H was induced by midline laparotomy and approximately 90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (four times the shed blood volume in the form of Ringer's lactate) [5].

Psychiatry related information on Mid1

• Static and dynamic views of retinal growth cones in this decision region reveal that extensive exploratory behavior and selective retraction of parts of the growing tips of uncrossed fibers, in response to cellular cues at the midline, is a major event in the guidance of these fibers [6].

High impact information on Mid1

• Pathfinding of retinal ganglion cell (RGC) axons at the midline optic chiasm determines whether RGCs project to ipsilateral or contralateral brain visual centers, critical for binocular vision [7].
• GAP-43-deficient retinal axons remain trapped in the chiasm for 6 days, unable to navigate past this midline decision point [8].
• The transcription factor gene HNF-3 beta is expressed in the ventral midline of the mouse embryonic neural tube, including the floor plate, a structure important for dorsoventral patterning and axonal guidance [9].
• Morphogenesis of the posterior midbrain was affected as early as embryonic day 16.5, leading to a reduction of the inferior colliculus near the midline and to altered foliation of the anterior cerebellum [10].
• Early defects are observed in the establishment or maintenance of midline structures, such as the notochord and the floorplate, and later defects include absence of distal limb structures, cyclopia, absence of ventral cell types within the neural tube, and absence of the spinal column and most of the ribs [11].

Chemical compound and disease context of Mid1

• The effects of Sim2s on transcriptional regulation through hypoxia, dioxin, and central midline response elements are different than that of full-length Sim2 [12].
• METHODS: Male C3H/HeN mice were subjected to a midline laparotomy and polyvinyl alcohol sponges were implanted subcutaneously in the abdominal wound before hemorrhage (35+/-5 mm Hg for 90 minutes and resuscitation) or sham operation [13].
• The folate metabolic enzyme ALDH1L1 is restricted to the midline of the early CNS, suggesting a role in human neural tube defects [14].
• Intact male mice (C3H/HeN), castrated males treated with vehicle, 5alpha-dihydrotestosterone (DHT), or 17beta-estradiol, and proestrous females were subjected to trauma (i.e., midline laparotomy) and hemorrhagic shock (35 +/- 5 mmHg for 90 min and resuscitation) or sham operation [15].
• In each study, after tumor cell injections, mice were randomly assigned to one of three groups: 1) anesthesia control (no procedure); 2) full laparotomy (4-cm midline incision x 20 minutes, staple closure); or 3) CO2 pneumoperitoneum (4-6 mmHg X 20 minutes) [16].

Biological context of Mid1

• Mid1 expression in undifferentiated cells in the central nervous, gastrointestinal and urogenital systems suggests that abnormal cell proliferation may underlie the defect in midline development characteristic of Opitz syndrome [17].
• Cooperation of sonic hedgehog enhancers in midline expression [18].
• The Fxy gene in mice is also located on the X chromosome but spans the pseudoautosomal boundary in this species [19].
• During embryogenesis, induction of these and other ventral neurons is influenced by interactions with the induction of mesoderm of the notochord and the floor plate, which lies at the ventral midline of the developing CNS [20].
• We investigated the consequences of the translocation further by sequencing exons and introns of Fxy in various rodent species [21].

Anatomical context of Mid1

• However, neither the midline expression of Sonic hedgehog nor the dorso-ventral patterning of the telencephalon was affected by Cdc42-deletion [22].
• The dependence of OPCs on retinal axonal cues appears to be a common phenomenon, because ocular retardation (or(J)) mice lacking optic nerve have dramatically reduced OPCs in the midline of the third ventricle [23].
• Developing axons of the corpus callosum of mice are guided across the cerebral midline by a slinglike glial structure that forms transiently between the hemispheres [24].
• These projections take a complex route during which they first cross the midline, then form the corticospinal tract, and ultimately connect with motor neurons in the contralateral side of the spinal cord [25].
• In striking contrast, the node and its midline derivatives, the notochord and floor plate, develop normally in both categories of mutant embryos [26].

Associations of Mid1 with chemical compounds

• Evidence from labeling growing retinal axons with the carbocyanine dye Dil in mouse embryos indicates that the two subpopulations diverge at a zone along the midline of the optic chiasm [27].
• We conclude that buildup of pre-cholesterol sterol intermediates interferes with midline fusion of facial structures in mice [1].
• Sites of 5-HT immunoreactivity were found in a variety of locations in tissues of the head and neck, which are either epithelia derived from the non-neural ectoderm or are non-neuronal midline brain structures [28].
• We concluded that the chondroitin sulfate moieties of the proteoglycans are involved in patterning the early phase of axonal growth across the midline and at a later stage controlling the axon divergence at the chiasm [29].
• PGE precursors and their neuronal descendants are organised into two polyclonal groups of similar sizes that exhibit parasagittal patterning and generally respect the midline [30].

Physical interactions of Mid1

• 125I-EGF binding sites were localized throughout the palate mesenchyme except in a region immediately adjacent to the midline seam [31].

Regulatory relationships of Mid1

• In zebrafish, as in other vertebrates, the secreted signalling molecule Sonic hedgehog (Shh) is expressed in organiser regions such as the embryonic midline and the zona limitans intrathalamica (zli) [18].
• Nodal signaling induces the midline barrier by activating Nodal expression in the lateral plate [32].
• At E12.5, Zic4 continues to be expressed in the midline of the forebrain and in the dorsal spinal neural tube [33].
• NFI-A protein is expressed in all three midline populations [34].
• Runx1 was also intensely expressed in the midline epithelium of palatal shelves [35].

Other interactions of Mid1

• Slit1 and Slit2 cooperate to prevent premature midline crossing of retinal axons in the mouse visual system [36].
• Gli2 mutants fail to develop a floor plate yet still develop motor neurons, which occupy the ventral midline of the neural tube [37].
• These results demonstrate that whereas Slit1 and Slit2 are not necessary for tangential migration of interneurons to the cortex, these proteins regulate neuronal migration within the basal telencephalon by controlling cell positioning close to the midline [38].
• Morphological and gene expression data further indicate that a functional midline is not maintained along the whole prosomere 1 in Msx1 mutant mice [39].
• The most probable cause for this left-right defect in Dll1 mutant embryos is a failure in the development of proper midline structures [40].

Analytical, diagnostic and therapeutic context of Mid1

• METHODS: Adult male mice (C57BL/6, CRF(1)-deficient, and wild-type), fasted for 16-18 hours, were anesthetized for 10 minutes and had a midline celiotomy and cecal exteriorization and palpation for 30 or 60 seconds or no surgery (sham) [41].
• Whole-mount in situ hybridization confirmed the dissection studies and demonstrated that Xwnt-4 transcripts are expressed in the dorsal midline of the midbrain, hindbrain and the floor plate of the neural tube [42].
• Injection of DiI into the node, and electroporation of a GFP expression vector into the midline neural plate, revealed defective convergent extension in both axial mesoderm and neuroepithelium, before the onset of neurulation [43].
• Male C3H/HeN mice underwent midline laparotomy (i.e., soft tissue injury), hemorrhagic shock (MAP approximately 35 mm Hg for 90 min), and resuscitation [44].
• Using immunocytochemistry, we also show that at E13.5, 5-HT-positive neurons in the midline extend over a larger rostro-caudal distance than at E11.5, and that in the presumptive initiating zone, cell bodies occupy a band that extends 200 mum laterally on each side of the midline, with extensive axonal processes [45].

References