Neural and skin cell‐specific expression pattern conferred by steel factor regulatory sequence in transgenic mice

Abstract

We have produced transgenic mice expressing a lac2 reporter gene under the control of a fragment of a Steel factor (SLF). The function of this gene is essential for the development of hematopoietic cells, germ cells, melanocytes and pacemaker cells of the intestine. The expression of the transgene, containing 2 kb DNA 5' regulatory sequence, was restricted to neural and skin tissues in appropriate spatial and temporal pattern compared with endogenous SLF mRNA expression. This indicates that the regulatory elements necessary for the neural and skin specific expression are present in this 2 kb DNA sequence, although strong position-dependence of transgene expression was observed, As we could not detect transgene expression in hematopoietic tissues and germ cells after extending 10 kb upstream, elements important for these organs must reside in other regions. Our results indicate that neural crest derived enteric ganglion cells provide SLF to the neighboring pace maker cells expressing c-kit, the receptor for SLF. Cells expressing the transgene in the intestine are ganglion cells derived from neural crest since homozygosity for the lethal spotting (Is) mutation results in loss of such ganglion cells in transgenic mice. We have also shown that the dermal papillae of the hair follicle expresses the transgene, suggesting its roles to support the c-kit dependent growth and development of melanocytes in the hair follicle. 0 1996 Wiley-Liss, Inc.

Two distinct types of mouse melanocyte: differential signaling requirement for the maintenance of non-cutaneous and dermal versus epidermal melanocytes

“…Horizontal serial sections were prepared at 3 μm and stained with Hematoxylin and Eosin (HE). lacZ staining lacZ staining was performed as reported in detail previously (Yoshida et al, 1996b). In brief, cells were fixed for 10 minutes in 2% paraformaldehyde supplemented with 0.2% glutaraldehyde and 0.02% Tween 20.…”

Stem Cells for Epidermal Melanocytes-A Challenge for Students of Dermatopathology

“…Today it is known that (1) stem cell factor is produced by human (but not mouse) epidermis and (2) stem cell factor supports melanocytic differentiation. [65][66][67][68] Stem cell factor acts by binding to the c-kit receptor, which may be demonstrated in immature and mature melanocytes in animal models. 67 In these studies, c-kit immunopositivity was demonstrated using snap-frozen acetone-fixed tissues and immunofluorescence, a method that is apparently more sensitive than the routine immunoperoxidase methods used on formalin-fixed paraffin-embedded tissue in routine practice in my Department.…”

On the Development of Neurocutaneous Units—Implications for the Histogenesis of Congenital, Acquired, and Dysplastic Nevi

“…[14][15][16] Nor is it known how nerves govern fetal skin healing without scarring. 17 It has been suggested that nerve sheath stem cells for melanocytes arrive in the skin during the process of embryonic cutaneous innervation, where exposure to epidermal stem cell factor induces melanocytic differentiaton via the c-kit receptor 16,18 (Appendix, Diagram 2). Nerve growth factor, basic fibroblast growth factor, and other substances may also play a role.…”