Mash1 regulates the development of C cells in mouse thyroid glands.
In mammals, the ultimobranchial body derived from the fourth pharyngeal pouch gives rise to thyroid C cells. The C cells of newborn mice are immunoreactive for calcitonin, calcitonin gene-related peptide (CGRP), protein gene product (PGP) 9.5 and NeuroD, and transiently exhibit the neuronal markers TuJ1 and somatostatin during fetal development. The basic helix-loop-helix (bHLH) transcription factor Mash1 plays a role in the differentiation of autonomic neurons. We show that in wild-type mouse embryos, Mash1 is expressed in the ultimobranchial body at embryonic day (E) 12.5, when the body is located close to the great arch arteries. It is also expressed in the ultimobanchial body fused with the thyroid lobe at E 13.5. Targeted disruption of Mash1 resulted in the absence of C cells in the mouse thyroid glands, since cells displaying the C-cell markers and expressing NeuroD were not detected during fetal development or at birth. The failure of C-cell formation in the null mutant thyroids was also confirmed by electron microscopy. While the formation and migration of the ultimobranchial body were not affected in the Mash1 null mutants, at E 12.5-E 13.5 both the ultimobranchial body located close to the arteries and the organ populating the thyroid lobe exhibited a marked increase in apoptotic cell numbers. Thus, in the mutant mice, the ultimobranchial body fails to complete its differentiation program and finally dies. These results indicate that Mash1 enhances survival of the C-cell progenitors by inhibiting apoptosis.
Kameda
Yoko
Y
Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. kameda@med.kitasato-u.ac.jp
Nishimaki
Toshiyuki
T
Miura
Masaaki
M
Jiang
Shin-Xu
SX
Guillemot
François
F
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002116:Calcitonin / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D013234:Stem Cells / Q000145:classification / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D014460:Ultimobranchial Body / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide; D009419:Nerve Tissue Proteins; C499317:Ascl1 protein, mouse; C093564:Neurogenic differentiation factor 1