HOXB5 expression is spatially and temporarily regulated in human embryonic gut during neural crest cell colonization and differentiation of enteric neuroblasts

Abstract

HOX genes from paralogous groups 4 and 5 are particularly relevant to the gut neuromusculature development because these genes are expressed at the splanchnic mesoderm surrounding the gut diverticulum, and at the level of the neural tube from where the vagal neural crest cells (NCCs) originate. In this study, we examined the migration and differentiation of NCCs, and investigated the expression patterns of HOXB5 in human embryonic guts. Human embryos of gestational week-4 to -8.5 were studied. Vagal NCCs enter the esophagus, migrate, and colonize the entire gut in a rostrocaudal manner between week-4 and week-7. The migrating NCCs in gut express HOXB5. Two separate and discontinuous mesenchymal expression domains of HOXB5 were detected in the gut: the distal domain preceding the migratory NCCs; and the proximal domain overlapping with the NCCs. The two expression domains shift caudally in parallel with the rostrocaudal migration of NCCs between week-4 and week-5. Neuron and glia differentiation of NCCs are concomitant with HOXB5 down-regulation in NCCs and the mesenchyme. By week-7, myenteric plexuses have formed; HOXB5 expression is switched on in the plexuses. We found that (1) the migratory route of NCCs in human embryonic gut was similar to that in mice and chicks; and (2) the expression pattern of HOXB5 correlated with the migration and differentiation of NCCs, suggesting a regulatory role of HOXB5 in the development of NCCs. Developmental Dynamics 228:1-10, 2003.

Hirschsprung disease: current perspectives

“…13 The more recent work of Fu et al 14 showed an earlier migration of vagal neuroblasts that colonize the entire gut in a rostrocaudal manner between weeks 4 and 7.…”

Ultrastructural analysis of the smooth‐to‐striated transition zone in the developing mouse esophagus: Emphasis on apoptosis of smooth and origin and differentiation of striated muscle cells

“…This proposal is supported by several results, which have been raised during the past years: (1) no migration of striated muscle precursor cells into the esophagus could be detected at E11.5 and later (Kablar et al, 2000); (2) at E11.5, the esophagus wall is built up of mesenchymal cells with no demarcation of layers (Kablar et al, 2000); (3) the myogenic transcription factor Myf5 was first detected at E12-E13 in the cranial esophagus, followed by MyoD and MRF4 at E14 and myogenin at E15 (Zhao and Dhoot, 2000b); (4) the expression of these myogenic factors, which are limited to skeletal muscle cells (Arnold and Braun, 2000), showed outer to inner layer and cranial to caudal progression during embryonic and early postnatal development of mouse esophagus (Kablar et al, 2000;Zhao and Dhoot, 2000b); (5) characteristic features of striated myogenesis, e.g., immunoreactivity for skeletal muscle specific myosin heavy chain or ␣-bungarotoxin-positive motor endplates, were first detected at approximately E14 -E15 in the cranial esophagus and showed also outer to inner layer and cranial to caudal progression (Sang and Young, 1997;Wörl and Neuhuber, 2000;Zhao and Dhoot, 2000a). It is tempting to speculate that MNC-I derive most likely from the same splanchnic mesoderm surrounding the primitive foregut, from which the smooth muscle cells of the developing esophagus originate (Roberts, 2000;Fu et al, 2003Fu et al, , 2004. The hypothesis that striated muscle precursors develop from autochthonous mesenchymal cells of the esophagus itself and do not migrate might provide the basis for a new concept of striated myogenesis.…”

“…Moreover, because at E11.5 the wall of the esophagus is still mesenchymal with no demarcation of layers and, furthermore, at this developmental stage and later no striated muscle progenitor cells migrating into the esophagus could be observed (Kablar et al, 2000), we considered that striated muscle progenitor cells might originate from the same splanchnic mesoderm surrounding the primitive foregut, from which the smooth muscle cells develop (Roberts, 2000;Fu et al, 2003Fu et al, , 2004. Therefore, they might already be present in the developing esophageal wall, when the striated myogenesis starts at E14.…”

Gastroschisis in Mice Lacking Aortic Carboxypeptidase-Like Protein Is Associated With a Defect in Neuromuscular Development of the Eviscerated Intestine

“…First, we used Hoxb5 a NCC marker (23). Our results suggest that, exposure to the AF results in a significant reduction of hoxb5 positive NCC within the EI.…”