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An. R. Acad. Nac. Farm., 2005, 71: 765-782

Revisión

Old hormones of the insulin family as new
developmental signals

FLORA DE PABLO*, 1, CATALINA HERNÁNDEZ-SÁNCHEZ1,
CARLOS VICARIO-ABEJÓN1, 2 AND ENRIQUE J. DE LA ROSA1
1 Group of Growth Factors in Vertebrate Development, Centro de

Investigaciones Biológicas (CSIC, Madrid).
2 Instituto Cajal (CSIC, Madrid)

ABSTRACT

Insulin was first identified as an anabolic pancreatic hormone responsible for
glucose homeostasis, and Insulin-like Growth Factor (IGF-I) as the mediator of the
action of Growth Hormone on postnatal growth. New molecular, pharmacological
and embryological information has broadened the scope of the physiological roles
of these hormones and their related molecules, particularly the insulin precursor
proinsulin, during vertebrate development. Studies in our laboratory have
demonstrated that proinsulin is expressed and functional before emergence of the
pancreas. Proinsulin gene expression in the chick and mouse embryo shows fine
transcriptional and postrancriptional regulation with generation of specific
embryonic transcripts which are differentially translated. The protein product
remains as unprocessed proinsulin that protects the cells from excessive apoptosis
during neurulation. In contrast, IGF-I is expressed later than proinsulin in the
chick embryo and it starts in the nervous system. In the mouse embryo, generation
of olfactory bulb stem cells in culture has allowed the study of these molecules’
role in the proliferation and differentiation of neural precursors. Proinsulin and
IGF-I can cooperate with mitogens (EGF and FGF2) in the control of stem/
precursor cells proliferation and IGF-I is an essential factor for neural
differentiation. Mice deficient in IGF-I present a disruption of olfactory bulb
cytoarchitecture, with decreased numbers of mitral cells and abnormal radial glia.
This article gives thus an overview of the important role of insulin family proteins
in development.

* Toma de Posesión como Académica Correspondiente, 4 de noviembre de 2004.

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