Tpit-independent function of NeuroD1(BETA2) in pituitary corticotroph differentiation.
NeuroD1(BETA2) and Tpit are cell-specific activators of pituitary proopiomelanocortin (POMC) gene transcription. Expression of both factors slightly precedes that of POMC at embryonic d 12.5 of mouse pituitary development. We now report that NeuroD1(BETA2) is required for early corticotroph differentiation. In agreement with the transcriptional synergism observed between Tpit and basic helix-loop-helix dimers containing NeuroD1(BETA2), POMC expression is delayed in NeuroD1-deficient mice. However, this differentiation defect does not reflect a change of corticotroph commitment as revealed by Tpit expression. The delay of corticotroph terminal differentiation is transient and coincides with the developmental window of NeuroD1 expression in corticotrophs. In contrast to their requirement in other NeuroD1-expressing cells, the neurogenin genes do not appear to be necessary for corticotroph differentiation. Taken together with a similar requirement of Tpit for corticotroph differentiation but not for commitment, the present data indicate that the POMC promoter is a point of convergence for independent corticotroph differentiating signals.
Lamolet
Bruno
B
Laboratoire de Génétique Moléculaire, Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, Québec, Canada H2W 1R7.
Poulin
Gino
G
Chu
Khoi
K
Guillemot
François
F
Tsai
Ming-Jer
MJ
Drouin
Jacques
J
D000324:Adrenocorticotropic Hormone / Q000172:deficiency; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000196:embryology*; D020825:T-Box Domain Proteins; D015534:Trans-Activators / Q000172:deficiency / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D000324:Adrenocorticotropic Hormone; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D020825:T-Box Domain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C501008:Neurod1 protein, mouse; C102938:Neurog2 protein, mouse; C424031:Tbx19 protein, mouse; C486336:Neurog1 protein, mouse