Biomedical subjects

L G Piñón

Publications and source records attributed to L G Piñón.

6 recordsLinked to original sources

PubMed1998

Bcl-2 accelerates the maturation of early sensory neurons.

Bcl-2 is a cytoplasmic protein that blocks apoptosis in a wide variety of cell types. Here we report a novel role for Bcl-2 in the early stages of neuronal development. Shortly after differentiating from progenitor cells, sensory neurons undergo a distinct morphological change; initially they have small, spindle-shaped, phase-dark cell bodies that become large, spherical, and phase-bright. Early sensory neurons cultured from the trigeminal ganglia of bcl-2-/- embryos at embryonic day 11 (E11) and E12 underwent this change more slowly than trigeminal neurons of wild-type embryos of the same ages. The delay was not attributable to the well documented role of Bcl-2 in preventing apoptosis, because Bcl-2-deficient early sensory neurons survived as well as wild-type neurons. Accordingly, there was a significantly smaller number of the more mature type of neuron in the early trigeminal ganglia of bcl-2-/- embryos, yet the number of neurons in the trigeminal ganglia of bcl-2-/- and wild-type embryos was similar. The absence of Bcl-2 did not cause a uniform delay in the developmental program of sensory neurons, because the time course of nerve growth factor receptor expression (both trkA and p75) was unaffected in the trigeminal neurons of bcl-2-/- embryos. These findings indicate that Bcl-2 expression is required for the normal progression of a particular early maturational change in embryonic sensory neurons.

Animals↗

PubMed1998

GFRalpha-4, a new GDNF family receptor.

GFRalpha-1, GFRalpha-2, and GFRalpha-3 constitute a family of structurally related, glycosyl-phosphatidylinosital-linked, cell surface proteins, two of which, GFRalpha-1 and GFRalpha-2, are components of the receptor complex for the neurotrophic factors GDNF and neurturin, respectively. By screening an embryonic chicken brain cDNA library with a GFRalpha-1 probe at low stringency, we isolated cDNAs encoding an additional member of the GFRalpha family, GFRalpha-4. The nucleotide sequence predicts a 431-amino-acid secreted protein that is more closely related to GFRalpha-1 and GFRalpha-2 than to GFRalpha-3. GFRalpha-4 mRNA is expressed in distinctive patterns in the brain and several other organs and tissues of the chicken embryo. Our findings extend the family of GFRalpha proteins and provide information about the tissues in which GFRalpha-4 may function during development.

Animals↗

PubMed1997

Neurturin responsiveness requires a GPI-linked receptor and the Ret receptor tyrosine kinase.

Neurturin (NTN) is a recently identified homologue of glial-cell-line-derived neurotrophic factor (GDNF). Both factors promote the survival of a variety of neurons, and GDNF is required for the development of the enteric nervous system and kidney. GDNF signals through a receptor complex consisting of the receptor tyrosine kinase Ret and a glycosyl-phosphatidylinositol (GPI)-linked receptor termed GDNFR-alpha. Here we report the cloning of a new GPI-linked receptor termed NTNR-alpha that is homologous with GDNFR-alpha and is widely expressed in the nervous system and other tissues. By using microinjection to introduce expression plasmids into neurons, we show that coexpression of NTNR-alpha with Ret confers a survival response to neurturin but not GDNF, and that coexpression of GDNFR-alpha with Ret confers a survival response to GDNF but not neurturin. Our findings indicate that GDNF and neurturin promote neuronal survival by signalling through similar multicomponent receptors that consist of a common receptor tyrosine kinase and a member of a GPI-linked family of receptors that determines ligand specificity.

Amino Acid Sequence↗

PubMed1997

Bcl-2 is required for cranial sensory neuron survival at defined stages of embryonic development.

To ascertain the role of endogenous Bcl-2 in maintaining the survival of developing neurons and modulating their responses to neurotrophins, we compared the in vitro and in vivo survival of cranial sensory neurons of wild-type and bcl-2 null mouse embryos. At the peak of naturally occurring neuronal death in the trigeminal ganglion at E14, trigeminal neurons from bcl-2(-/-) embryos initially survived in culture in response to NGF but were not sustained as well as neurons from wild-type embryos. At the end of the period of naturally occurring neuronal death at E18, Bcl-2-deficient trigeminal neurons survived with NGF as well as wild-type neurons. At E14 in vivo, the number of trigeminal neurons undergoing apoptosis was significantly greater in bcl-2(-/-) embryos, and there were significantly fewer neurons in the trigeminal ganglia of bcl-2(-/-) embryos at E16 and E18. Similar age-related changes in the responses of nodose ganglion neurons to BDNF were observed in cultures established from bcl-2(-/-) and wild-type embryos between E14 and E18. These results suggest that endogenous Bcl-2 is required for the sustained survival response of a subset of cranial sensory neurons to neurotrophins at particular stages of embryonic development and show that its absence leads to reduced numbers of these neurons in vivo.

Animals↗

PubMed1996

Expression and function of TrkB variants in developing sensory neurons.

Mouse trigeminal neurons survive independently of neurotrophins when their axons are growing to their targets, and are then transiently supported by BDNF before becoming NGF dependent. During the stage of neurotrophin independence, transcripts encoding the BDNF receptor, TrkB, were expressed at very low levels. During the stage of BDNF dependence, high levels of a transcript encoding a receptor with the catalytic tyrosine kinase domain were expressed. Although the levels of this transcript fell as the neurons lost responsiveness to BDNF, there were concomitant increases in the expression of transcripts encoding TrkB variants lacking the kinase domain. Analysis of RNA from purified neurons showed that all of these transcripts were present in neurons. BDNF and NGF up-regulated the expression of these transcripts early in development but had little effect later on. To test whether truncated TrkB modulates BDNF signalling via catalytic TrkB, we injected TrkB expression plasmids into NGF-dependent sympathetic neurons. Whereas expression of catalytic TrkB alone conferred a BDNF survival response, co-expression of non-catalytic TrkB substantially reduced this response. Our results suggest that BDNF responsiveness in sensory neurons during development is modulated by the relative levels of catalytic and non-catalytic TrkB.

Animals↗

PubMed1996

Target and afferents interact to control developmental cell death in the mesencephalic parabigeminal nucleus of the rat.

During the period of natural cell death in the developing mammalian brain, both target cells and afferents have been shown to be important for neuronal survival. Here we demonstrate that afferents and targets have interactive roles in the maintenance of cells during development of the mesencephalic parabigeminal nucleus (PB) in rats. Pyknotic nuclei were counted in the PB of developing rats that received a bilateral lesion of the superior colliculus on the day of birth (P0). We observed that simultaneous deafferentation and deeferentation leads to a large peak of cell death at P1-2 in all three divisions of PB. Later the rate of pyknosis decreases and a second period of elevated cell death is observed just before the complete disappearance of the nucleus at P7-8. Counts of healthy neurones indicates two separate periods of increased neuronal loss. The first period occurs at P1-2, and the last and dramatic episode of cell loss at P8 leads to the disappearance of the PB. The combined effects of simultaneous target removal and deafferentation were different from the sum of the individual effects, indicating that the axonal targets and the afferents interact to control cell survival in the PB.

Afferent Pathways↗