Biomedical subjects

Carmen Fernández-Moreno

Publications and source records attributed to Carmen Fernández-Moreno.

5 recordsLinked to original sources

PubMed2004

Mice lacking IGF-I and LIF have motoneuron deficits in brain stem nuclei.

We analyzed the neural embryonic phenotype of single and double-mutant mice for insulin-like growth factor-I (IGF-I) and leukemia inhibitory factor (LIF). The anatomical structure of the hippocampus, the cerebellum, and the olfactory epithelium, regions showing expression of both factors and their receptors, appeared largely normal in all mutant mice. In the fimbria and the spinal cord, similar patterns of glial fibrillary acidic protein (GFAP)-expressing astrocytes were found in wild-type and mutant mice. In contrast, single Igf-I and double-mutant mice showed a significant reduction in the number of trigeminal and facial motoneurons, whereas mice lacking LIF showed a significant reduction of trigeminal motoneurons. These results suggest that IGF-I and LIF regulate cooperatively motoneuron numbers in specific brain stem nuclei.

Animals↗

PubMed2004

Increased leptin and white adipose tissue hypoplasia are sexually dimorphic in Lif null/Igf-I haploinsufficient mice.

We previously showed cooperation of leukemia inhibitory factor (LIF) and insulin-like growth factor I (IGF-I) during development. Mice doubly deficient in LIF and IGF-I died at birth. We now analyze the possible combined influence of both factors on postnatal growth. The haploinsufficiency of the Igf-I gene on a Lif null background caused a marked reduction in body mass index and white adipose tissue only in female mice. These animals had increased leptin, increased serum IGF-I and apparent substitution of white adipose tissue by brown adipose tissue. The complex interrelationships between LIF and IGF-I in regulating weight thus involve sexually dimorphic effects on adipose tissue differentiation and circulating leptin.

Adipose Tissue↗

PubMed2003

Locally born olfactory bulb stem cells proliferate in response to insulin-related factors and require endogenous insulin-like growth factor-I for differentiation into neurons and glia.

After late embryogenesis, new neurons are continuously added to the olfactory bulb (OB) from stem cells located in the forebrain subventricular zone. Nonetheless, stem cells have not been described within the embryonic olfactory bulb. Here we report the isolation of local olfactory bulb stem cells from the embryonic day 12.5-14.5 mouse embryo. These cells were 99.2% nestin positive and proliferated extensively in culture to at least 150 cell doublings. Clonal analysis demonstrated that neurons (TuJ1(+)), astrocytes (GFAP(+)), and oligodendrocytes (O4(+)) could be generated from single-plated cells, indicating that they are multipotent. At least 90% of proliferating cells expressed insulin-like growth factor-I (IGF-I), (pro)insulin, and their cognate receptors; these growth factors collaborated with fibroblast growth factor-2 plus epidermal growth factor (EGF) to promote stem cell proliferation and sphere formation. Cells from Igf-I(-)/- mice, however, proliferated as extensively as did Igf-I(+/+) cells. Differentiation and survival of stem cell-generated neurons and glia showed strong dependence on exogenous IGF-I, but oligodendrocyte differentiation also required insulin at low concentration. Furthermore, the percentages of stem cell-generated neurons, astrocytes, and oligodendrocytes were markedly lower in the cultures prepared from the Igf-I(-)/- mice compared with those of Igf-I(+/+). Concordantly, lack of IGF-I resulted in abnormal formation of the olfactory bulb mitral cell layer and altered radial glia morphology. These results support the presence within the embryonic mouse olfactory bulb of stem cells with specific requirements for insulin-related growth factors for proliferation or differentiation. They demonstrate that IGF-I is an endogenous factor regulating the differentiation of stem and other precursor cells within the olfactory bulb.

Animals↗

PubMed2003

Developmental cooperation of leukemia inhibitory factor and insulin-like growth factor I in mice is tissue-specific and essential for lung maturation involving the transcription factors Sp3 and TTF-1.

The multifunctional proteins leukemia inhibitory factor (LIF) and insulin-like growth factor I (IGF-I) are expressed in overlapping patterns during development and, therefore, may act cooperatively. We show that mice doubly deficient in LIF and IGF-I all died at birth of apparent respiratory failure. Growth retardation, muscle hypoplasia and delayed ossification in IGF-I-deficient E18.5 mice were exacerbated by the absence of LIF. The transcription factor Sp3 was decreased in the skeleton of the double null mice. Pronounced depletion of olfactory bulb neurons, in contrast, was only IGF-I-dependent. The lungs displayed reduced air space in the IGF-I-deficient embryos and neonates, phenotype exacerbated in the double nulls, which showed abnormal epithelial cells and decreased Sp3 expression. In addition, the transcription factor TTF-1 and the surfactant protein B were lower in the lung of the double null neonates than in all other genotypes. LIF and IGF-I, thus, have cooperative and distinct tissue functions during development. Their essential role in bone ossification apparently involves Sp3, and in lung maturation Sp3 together with TTF-1.

Animals↗

PubMed2002

Cochlear abnormalities in insulin-like growth factor-1 mouse mutants.

Insulin-like growth factor 1 (IGF-1) modulates inner ear cell proliferation, differentiation and survival in culture. Its function in human hearing was first evidenced by a report of a boy with a homozygous deletion of the Igf-1 gene, who showed severe sensorineural deafness [Woods et al., New Engl. J. Med. 335 (1996) 1363-1367]. To better understand the in vivo role of IGF-1 during inner ear differentiation and maturation, we studied the cochleae of Igf-1 gene knockout mice by performing morphometric stereological analyses, immunohistochemistry and electron microscopy on postnatal days 5 (P5), P8 and P20. At P20, but not at P5, the volumes of the cochlea and cochlear ganglion were significantly reduced in mutant mice, although the reduction was less severe than whole body dwarfism. A significant decrease in the number and average size of auditory neurons was also evident at P20. IGF-1-deficient cochlear neurons showed increased apoptosis, along with altered expression of neurofilament 200 kDa and vimentin. The eighth nerve, the cochlear ganglion and the fibers innervating the sensory cells of the organ of Corti of the P20 mouse mutants presented increased expression of vimentin, whereas the expression of neurofilament was decreased. In addition, the myelin sheath was severely affected in ganglion neurons. In conclusion, IGF-1 deficit in mice severely affects postnatal survival, differentiation and maturation of the cochlear ganglion cells.

Aging↗