The proneural gene ascl1a is required for endocrine differentiation and cell survival in the zebrafish adenohypophysis.
Mammalian basic helix-loop-helix proteins of the achaete-scute family are proneural factors that, in addition to the central nervous system, are required for the differentiation of peripheral neurons and sensory cells, derivatives of the neural crest and placodal ectoderm. Here, in identifying the molecular nature of the pia mutation, we investigate the role of the zebrafish achaete-scute homologue ascl1a during development of the adenohypophysis, an endocrine derivative of the placodal ectoderm. Similar to mutants deficient in Fgf3 signaling from the adjacent ventral diencepahalon, pia mutants display failure of endocrine differentiation of all adenohypophyseal cell types. Shortly after the failed first phase of cell differentiation, the adenohypophysis of pia mutants displays a transient phase of cell death, which affects most, but not all adenohypophyseal cells. Surviving cells form a smaller pituitary rudiment, lack expression of specific adenohypophyseal marker genes (pit1, neurod), while expressing others (lim3, pitx3), and display an ultrastructure reminiscent of precursor cells. During normal development, ascl1a is expressed in the adenohypophysis and the adjacent diencephalon, the source of Fgf3 signals. However, chimera analyses show that ascl1a is required cell-autonomously in adenohypophyseal cells themselves. In fgf3 mutants, adenohypophyseal expression of ascl1a is absent, while implantation of Fgf3-soaked beads into pia mutants enhances ascl1a, but fails to rescue pit1 expression. Together, this suggests that Ascl1a might act downstream of diencephalic Fgf3 signaling to mediate some of the effects of Fgf3 on the developing adenohypophysis.
Max-Planck Institute of Immunobiology, 79108 Freiburg, Germany.
Hans-Martin
HM
Pogoda
Sophia
S
von der Hardt
Wiebke
W
Herzog
Carina
C
Kramer
Heinz
H
Schwarz
Matthias
M
Hammerschmidt
D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002470:Cell Survival; D004027:Diencephalon / Q000196:embryology / Q000378:metabolism; D004703:Endocrine System / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D051518:Fibroblast Growth Factor 3 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D014157:Transcription Factors; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D051518:Fibroblast Growth Factor 3; D014157:Transcription Factors; D029961:Zebrafish Proteins; C468127:Ascl1a protein, zebrafish; C489200:fgf3 protein, zebrafish