The role of Phox2B in chromaffin cell development.
Phox2B, a homeodomain transcription factor closely related to Phox2A, is expressed in peripheral and central noradrenergic neurons. In neural crest (NC) derivatives Phox2B is restricted to sympathetic and parasympathetic ganglia, enteric neurons, and adrenal and extraadrenal chromaffin cells. Similar to MASH-1, Phox2B has been implicated in synchronizing pan-neuronal and catecholaminergic phenotype-specific aspects of neurogenesis. The role of Phox2B for the differentiation of the neuroendocrine NC derivatives, the adrenal medullary chromaffin cells, has not been explored. We have previously reported that in MASH-1-deficient mice most chromaffin cells are arrested at the early neuroblast stage and lack catecholaminergic differentiation. We show now that in Phox2B knockout/lacZ knockin mice the maturation of presumptive chromaffin cells is arrested at an even earlier stage of development. The cells lack the catecholaminergic marker enzyme TH and fail to form a centrally located medulla. In contrast to MASH-1 (-/-) mice they do not express dHand, Phox2A, c-ret, neurofilament, neuron-specific tubulin, and NCAM and appear ultrastructurally more immature. Many of these cells die by apoptosis. Despite the complete lack of differentiation, few lacZ-positive adrenal cells can still be found at E16.5. We conclude that Phox2B regulates very early events in the differentiation of adrenal chromaffin cells distinct to steps, which essentially require MASH-1.
Huber
Katrin
K
Neuroanatomy, Interdisciplinary Center for Neurosciences, University of Heidelberg, INF 307, D-69120 Heidelberg, Germany. katrin.huber@ana.uni-heidelberg.de
Karch
Nicole
N
Ernsberger
Uwe
U
Goridis
Christo
C
Unsicker
Klaus
K
D000311:Adrenal Glands / Q000033:anatomy & histology / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology*; D019439:Chromaffin Cells / Q000166:cytology / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D013234:Stem Cells / Q000378:metabolism / Q000648:ultrastructure; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C109220:NBPhox protein