During early development in vertebrates, Sonic hedgehog (Shh) is produced by the notochord and the floor plate. A ventrodorsal gradient of Shh directs ventrodorsal patterning of the neural tube. However, Shh is also required for the survival of neuroepithelial cells. We show that Patched (Ptc) induces apoptotic cell death unless its ligand Shh is present to block the signal. Moreover, the blockade of Ptc-induced cell death partly rescues the chick spinal cord defect provoked by Shh deprivation. Thus, the proapoptotic activity of unbound Ptc and the positive effect of Shh-bound Ptc on cell differentiation probably cooperate to achieve the appropriate spinal cord development.

The relationships between notochord and floor plate in vertebrate development revisited

The human KAL gene is responsible for the X chromosome-linked Kallmann syndrome. A partial cDNA sequence from the chicken KAL homologue was determined and used to study expression of the KAL gene, by in situ hybridization, during chicken development, from day 6 of incubation. The KAL gene is mainly expressed in neurons of the central nervous system during the second half of embryonic life. High levels of transcript were detected in mitral neurons of the olfactory bulbs, in striatal neurons, in Purkinje cells of the cerebellum, in retinal neurons, and in isolated neurons of the brainstem and spinal cord. No expression was observed in glial cells. A low level of expression was observed in some mesenchymal derivatives. In the adult, expression is maintained or increased in several neuronal populations, especially in optic tectum and striatum. A possible role for the KAL protein in synaptogenesis at these stages is discussed. These results in the chicken embryo help to elucidate the mechanisms of anosmia and gonadotropin-releasing hormone deficiency, which define Kallmann syndrome. In addition, most of the occasional symptoms described in Kallmann syndrome patients, such as cerebellar ataxia, abnormal ocular movements, abnormal spatial visual attention, mirror movements, and renal aplasia, could be ascribed to malfunction of areas that, in the chicken, express the KAL gene.Kallmann syndrome (KS) is an inherited disease defined by the association of hypogonadotropic hypogonadism and anosmia (absence of the sense of smell). The hypogonadism is due to a deficiency in gonadotropin-releasing hormone (GnRH) (1) and the anosmia has been related to aplasia of the olfactory bulbs and olfactory tracts (2). A positional cloning strategy was used to isolate the gene responsible for the X chromosome-linked form of the disease (KAL gene) (3)(4)(5) Embryological studies in several species (9-11), including chicken (12, 13), have established that GnRH-synthesizing neurons derive from the olfactory placodes. In mammals, three other types of neurons-namely, the nervus terminalis, the olfactory, and the vomeronasal neurons-derive from the olfactory epithelium. Their axons reach, respectively, the preoptic area, the olfactory bulbs, and the accessory olfactory bulbs and form a bridge of neural cell adhesion molecule immunoreactive fibers between the olfactory pit and the developing forebrain. GnRH neurons, which originate from the same part of the olfactory pit as the vomeronasal and terminalis nerves, leave the olfactory epithelium, migrating to the brain along these nerves, and ultimately reach the preoptic and hypothalamic areas (14). Histological analysis of a human male fetus carrying a deletion of the KAL gene has revealed that neither the GnRH neurons nor the axon terminals of the olfactory, terminalis, and vomeronasal neurons were present in the brain (15). This observation can account for the absence of olfactory bulbs in KS patients, since contact between the ingrowing olfactory axons and the forebrain is required for...