Progressive impairment of developing neuroendocrine cell lineages in the hypothalamus of mice lacking the Orthopedia gene

被引:156
作者
Acampora, D
Postiglione, MP
Avantaggiato, V
Di Bonito, M
Vaccarino, FM
Michaud, J
Simeone, A
机构
[1] CNR, Int Inst Genet & Biophys, I-80125 Naples, Italy
[2] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA
[3] Univ Montreal, Hop St Justine, Serv Genet Med, Montreal, PQ H3T 1C5, Canada
关键词
Orthopedia; cell migration; cell proliferation; neuroendocrine hypothalamus; terminal differentiation;
D O I
10.1101/gad.13.21.2787
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Development of the neuroendocrine hypothalamus is characterized by a precise series of morphogenetic milestones culminating in terminal differentiation of neurosecretory cell lineages. The homeobox-containing gene Orthopedia (Otp) is expressed in neurons giving rise to the paraventricular (PVN), supraoptic (SON), anterior periventricular (aPV), and arcuate (ARN) nuclei throughout their development. Homozygous Otp(-/-) mice die soon after birth and display progressive impairment of crucial neuroendocrine developmental events such as reduced cell proliferation, abnormal cell migration, and failure in terminal differentiation of the parvocellular and magnocellular neurons of the aPV, PVN, SON, and ARN. Moreover, our data provide evidence that Otp and Sim1, a bHLH-PAS transcription factor that directs terminal differentiation of the PVN, SON, and aPV, act in parallel and are both required to maintain Brn2 expression which, in turn, is required for neuronal cell lineages secreting oxytocin (OT), arginine vasopressin (AVP), and corticotropin-releasing hormone (CRH).
引用
收藏
页码:2787 / 2800
页数:14
相关论文
共 39 条
  • [1] Acampora D, 1998, DEVELOPMENT, V125, P1229
  • [2] MODEL OF FOREBRAIN REGIONALIZATION BASED ON SPATIOTEMPORAL PATTERNS OF POU-III HOMEOBOX GENE-EXPRESSION, BIRTH-DATES, AND MORPHOLOGICAL FEATURES
    ALVAREZBOLADO, G
    ROSENFELD, MG
    SWANSON, LW
    [J]. JOURNAL OF COMPARATIVE NEUROLOGY, 1995, 355 (02) : 237 - 295
  • [3] AVANTAGGIATO V, 1995, J NEUROSCI, V15, P4927
  • [4] P-LIM, A LIM HOMEODOMAIN FACTOR, IS EXPRESSED DURING PITUITARY ORGAN AND CELL COMMITMENT AND SYNERGIZES WITH PIT-1
    BACH, I
    RHODES, SJ
    PEARSE, RV
    HEINZEL, T
    GLOSS, B
    SCULLY, KM
    SAWCHENKO, PE
    ROSENFELD, MG
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (07) : 2720 - 2724
  • [5] A family of LIM domain-associated cofactors confer transcriptional synergism between LIM and Otx homeodomain proteins
    Bach, I
    Carriere, C
    Ostendorff, HP
    Andersen, B
    Rosenfeld, MG
    [J]. GENES & DEVELOPMENT, 1997, 11 (11) : 1370 - 1380
  • [6] THE PITUITARY-SPECIFIC TRANSCRIPTION FACTOR-GHF-1 IS A HOMEOBOX-CONTAINING PROTEIN
    BODNER, M
    CASTRILLO, JL
    THEILL, LE
    DEERINCK, T
    ELLISMAN, M
    KARIN, M
    [J]. CELL, 1988, 55 (03) : 505 - 518
  • [7] BULFONE A, 1993, J NEUROSCI, V13, P3155
  • [8] SPECIFICATION OF LIMB DEVELOPMENT IN THE DROSOPHILA EMBRYO BY POSITIONAL CUES FROM SEGMENTATION GENES
    COHEN, SM
    [J]. NATURE, 1990, 343 (6254) : 173 - 177
  • [9] ONTOGENY OF THE CALCIUM-BINDING PROTEIN CALBINDIN D-28K IN THE RAT NERVOUS-SYSTEM
    ENDERLIN, S
    NORMAN, AW
    CELIO, MR
    [J]. ANATOMY AND EMBRYOLOGY, 1987, 177 (01): : 15 - 28
  • [10] Felig P., 1987, Endocrinology Metabolism, V2nd Ed