mKlf7, a potential transcriptional regulator of TrkA nerve growth factor receptor expression in sensory and sympathetic neurons

Development of the nervous system relies on stringent regulation of genes that are crucial to this process. TrkA, the receptor for nerve growth factor (NGF), is tightly regulated during embryonic development and is essential for the survival and differentiation of neural crest-derived sensory and sympathetic neurons. We have previously identified a mouse TrkA enhancer and have characterized several cis regulatory elements that are important for appropriate TrkA expression in vivo. We now report the cloning of a novel gene encoding a Kruppel-like factor from a mouse dorsal root ganglion expression library. This Kruppel-like factor, named mKlf7, binds specifically to an Ikaros core binding element that is crucial for in vivo TrkA enhancer function. Using in situ hybridization, we demonstrate that mKlf7 is coexpressed with TrkA in sensory and sympathetic neurons during embryogenesis and in adulthood. These data are consistent with the idea that mKlf7 may directly regulate TrkA gene expression in the peripheral nervous system.

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Immunohistochemical analysis of nerve growth factor receptor expression in normal and malignant human tissues.

Journal of Histochemistry & Cytochemistry ◽

10.1177/36.4.2831267 ◽

1988 ◽

Vol 36 (4) ◽

pp. 383-389 ◽

Cited By ~ 91

Author(s):

P G Chesa ◽

W J Rettig ◽

T M Thomson ◽

L J Old ◽

M R Melamed

Keyword(s):

Nervous System ◽

Nerve Growth Factor ◽

Growth Factor ◽

Normal Development ◽

Malignant Tumors ◽

Sympathetic Neurons ◽

Growth Factor Receptor ◽

Nerve Growth Factor Receptor ◽

Receptor Expression ◽

Nerve Growth

Nerve growth factor (NGF) is a polypeptide important for normal development of the nervous system and promotion of survival and differentiation of sensory and sympathetic neurons in culture. The cellular effects of NGF are mediated by a specific cell surface molecule, nerve growth factor receptor (NGF-R). In the present study we have used a monoclonal antibody against human NGF-R to examine, by the avidin-biotin-immunoperoxidase method, the receptor distribution in a wide range of normal tissues and in more than 200 malignant tumors. Our results show that (a) human NGF-R is expressed in the peripheral nervous system but not in any of the central nervous system areas tested; (b) NGF-R expression is not restricted to neural tissues but is also found in a number of normal epithelial, mesenchymal, and lymphoid tissues; (c) NGF-R expression changes during normal development; and (d) NGF-R expression in malignant tumors generally parallels its normal tissue distribution. Thus, NGF-R is detected in a proportion of neuroectoderm-derived tumors, carcinomas, and lymphomas, and also in a characteristic group of small round-cell tumors (Ewing's sarcomas and embryonal rhabdomyosarcomas). These findings suggest a normal regulatory role for NGF in both neuronal and non-neuronal cells and identify a range of human tumors in which the NGF/NGF-R system may contribute to the malignant phenotype.

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Expression of the nerve growth factor-regulated NGFI-A and NGFI-B genes in the developing rat

Development ◽

10.1242/dev.110.1.173 ◽

1990 ◽

Vol 110 (1) ◽

pp. 173-183 ◽

Cited By ~ 1

Author(s):

M.A. Watson ◽

J. Milbrandt

Keyword(s):

Nervous System ◽

Nerve Growth Factor ◽

Growth Factor ◽

Peripheral Nervous System ◽

Receptor Expression ◽

Nerve Growth ◽

Postnatal Maturation ◽

System A ◽

Neuronal Tissues

NGFI-A and NGFI-B are two genes that are induced in PC12 cells treated with nerve growth factor and encode zinc-finger proteins that may act as transcription factors. To study the function of these genes in vivo, their expression in rat embryos and postnatally developing tissues was examined. Both genes are expressed during embryogenesis from E12 to E18. In postnatally developing animals, these genes are induced in cortex, midbrain and cerebellum, suggesting that they may function in one or many of the changes that occur during postnatal maturation of the brain. Both genes are expressed at a low, constitutive level in a subset of other non-neuronal tissues, but also demonstrate developmental changes in expression in many other organs. To examine expression of these genes in ganglia of the peripheral nervous system, a sensitive and quantitative assay employing reverse transcription and polymerase chain reaction was developed. Results obtained with this assay demonstrated that expression of both NGFI-A and NGFI-B is modulated in the peripheral nervous system during postnatal maturation, but not in a pattern concordant with previously characterized NGF receptor expression. These studies suggest that NGFI-A and NGFI-B serve multiple, tissue-specific functions and are under complex regulation in vivo.

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