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VOL. 71 (4), 765-782, 2005 OLD HORMONES OF THE INSULIN...

TABLE I. Developmental abnormalities induced by proinsulin excess

in E1,5 chick embryos
py

Control embryos abnormal Nº of embryos
Proinsulin treated embryos abnormal 0 /13
12/15

Abnormalities: 5/15
Asymmetric anterior neuropore closure 8/15
Flattened optic vesicles 6/15
Asymmetric rhombomers 9/15
Neural tube flexures

Reduction of apoptosis in proinsulin 5/5
treated embryos:

From Hernández-Sánchez et al. 2003

IGF-I is essential for differentiation of neural stem/precursor
cells in mice

After the progress made in understanding an early developmental
role of proinsulin, it did not escape our attention that most
investigators in the field of growth and development had analysed
the possible roles of two other proteins of the family, IGF-I and II,
in much more depth. Experiments using gene targeting deletion
approaches generated mice lacking expression of IGF-I and II, and
their receptors, alone or in combination, over a decade ago. Together
with the confirmation of the essential role of each of these two
factors in prenatal growth -in addition to IGF-I’s role in postnatal
growth, which has led to its use in human therapy (35) emerged
evidence of a variety of subtle phenotypes in different tissues (3,
23, 27). From our previous studies in chick embryos we knew that
IGF-I was expressed earlier during organogenesis in the nervous
system than in other tissues; the availability of IGF-I knockout mice
convinced us to switch to this model for a detailed analysis of the
role of IGF-I in neurogenesis.

To set out a suitable system for manipulation we established
highly proliferative cultures with the self-renewal characteristics of
stem cells (39), obtained from the olfactory bulb of embryonic E12.5

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