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Anosmin‐1 is a regionally restricted component of basement membranes and interstitial matrices during organogenesis: Implications for the developmental anomalies of X chromosome‐linked Kallmann syndrome
Author(s) -
Hardelin JeanPierre,
Julliard A. Karyn,
Moniot Brigitte,
SoussiYanicostas Nadia,
Verney Catherine,
SchwanzelFukuda Marlene,
AyerLe Lievre Christiane,
Petit Christine
Publication year - 1999
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/(sici)1097-0177(199905)215:1<26::aid-dvdy4>3.0.co;2-d
Subject(s) - kallmann syndrome , biology , olfactory bulb , anatomy , olfactory system , organogenesis , hypogonadotropic hypogonadism , forebrain , olfactory marker protein , microbiology and biotechnology , endocrinology , neuroscience , medicine , genetics , central nervous system , hormone , gene , disease , covid-19 , infectious disease (medical specialty)
Kallmann syndrome is a developmental disease characterized by gonadotropin‐releasing hormone (GnRH) deficiency and olfactory bulb hypoplasia. The gene underlying the X chromosome‐linked form, KAL‐1 , has been identified for several years, yet the pathogenesis of the disease is not understood. By immunohistofluorescence and immunoelectron microscopy, we establish that the KAL‐1 encoded protein, anosmin‐1, is a transient and regionally restricted component of extracellular matrices during organogenesis in man. Anosmin‐1 was detected in the basement membranes and/or interstitial matrices of various structures including bronchial tubes, mesonephric tubules and duct, branches of the ureteric bud, muscular walls of the digestive tract and larger blood vessels, precartilaginous models of skeletal pieces, muscle tendons, head mesenchymes, inner ear, and forebrain subregions. Our results suggest that this protein acts as a local, rather than a long‐range, cue during organogenesis. In the olfactory system, anosmin‐1 was detected from week 5 onward. The protein was restricted to the olfactory bulb presumptive region and later, to the primitive olfactory bulbs. We therefore suggest that the genetic defect underlying X‐linked Kallmann syndrome disrupts the terminal navigation of the early olfactory axons or directly affects the initial steps of olfactory bulb differentiation. The mechanism of the GnRH deficiency is also discussed, relying on the evidence that anosmin‐1 is present in the medial walls of the primitive cerebral hemispheres, along the rostro‐caudal migratory pathway of the GnRH‐synthesizing neurons, at 6 weeks. Finally, the present results strongly suggest that the renal aplasia observed in about one third of the affected individuals results from primary failure of the collecting duct system. Dev Dyn 1999;215:26–44 . © 1999 Wiley‐Liss, Inc.