EXTREMITIES/abnormalities Dotaz Zobrazit nápovědu

Přesná shoda

BACKGROUND: The thalidomide disaster resulted in tremendous congenital malformations in more than 10,000 children in the late 1950s and early 1960s. SUMMARY: Although numerous putative mechanisms were proposed to explain thalidomide teratogenicity, it was confirmed only recently that thalidomide, rather its derivative 5-hydroxythalidomide (5HT) in a complex with the cereblon protein, interferes with early embryonic transcriptional regulation. 5HT induces selective degradation of SALL4, a principal transcriptional factor of early embryogenesis. Genetic syndromes caused by pathogenic variants of the SALL4 gene phenocopy thalidomide embryopathy with congenital malformations ranging from phocomelia, reduced radial ray, to defects of the heart, kidneys, ear, eye, and possibly cerebral midline and pituitary. SALL4 interacts with TBX5 and a handful of other transcriptional regulators and downregulates the Sonic hedgehog signaling pathway. Cranial midline defects, microcephaly, and short stature due to growth hormone deficiency have been occasionally reported in children carrying SALL4 pathogenic variants associated with generalized stunting of growth rather than just the loss of height attributable to the shortening of leg bones in many children with thalidomide embryopathy. KEY MESSAGES: Thus, SALL4 joins the candidate gene list for monogenic syndromic pituitary insufficiency. In this review, we summarize the journey from the thalidomide disaster through the functions of the SALL4 gene to its link to the hormonal regulation of growth.

Klíčová slova
Embryogenesis, Limb development, Pituitary development, SALL4, Thalidomide,
MeSH
horní končetina MeSH
lidé MeSH
mnohočetné abnormality * chemicky indukované genetika MeSH
nemoci plodu * MeSH
proteiny hedgehog MeSH
thalidomid * škodlivé účinky MeSH
transkripční faktory * genetika MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
přehledy MeSH
Názvy látek
proteiny hedgehog MeSH
SALL4 protein, human MeSH Prohlížeč
thalidomid * MeSH
transkripční faktory * MeSH

Článek

Significance of the differential growth, relative tissue shifts and the vascular bed in limb development

Seichert, V
Autor Seichert, V Department of Anatomy, Charles University Medical Faculty, Prague, Czechoslovakia

Acta Universitatis Carolinae. Medica. Monographia. 1988 ; 125 () : 1-162.

Acta Univ Carol Med Monogr
ISSN 0567-8250
Zdroj

1. A method for planimetric measurement of areas of standardized dorsoventral projections of embryonal limbs was elaborated. The method permits a quantitative study of the growth of embryonic limbs at early stages of development, since the stage of flat limb bud until the stage at which the external shape of the limb (bending in joint regions and increase in volume) interferes with the simplification of its three-dimensional characteristics to two-dimensional ones of its dorsoventral projection. (Until stage 31-32HH for the chick embryo, see fig. 1 and 2). 2. A method of linear marking was elaborated (fig. 3). The marker proper are India-ink particles suspended in gelatin. Such stained gelatin is spread over a glass carrier (a glass fibre 10-20 microns thick) in the form of a thin film. After drying the fibre is cut in rods of a length desired for the appropriate linear mark. The marks can be introduced into the tissue by a single stab. After the gelatin film had swollen owing to the presence of tissue fluids, it is detached from the carrier surface and the carrier can be removed from the tissue. After the gelatin had been resorbed, a linear mark remains in the tissue. Deformations of the mark line and the scattering of India-ink particles which actually form the mark facilitates the assessment of the growth pattern of the respective marked tissue (see fig. 4-6). 3. During our studies of the differential growth of the wing bud with the method of linear marking the newly coined term "relative tissue shift" had to be specified. That term has been used for designating changes of the mutual position of tissue areas which could not be defined exactly as to their topography within a region or organ (such as the wing bud), showing fluent transitions between one another. If areas with different growth activities occur in the region studied, such areas undergo an uneven increase (differential growth). Thus another factor is added to those operating in the growth process, namely the direction of expansion of the different growing areas of the region studied to one another. The resultant of the mutual ratios of the voluminal growth of the neighbouring tissue areas and the directions of their expansion are the relative tissue shifts in the sense used in our studies.(ABSTRACT TRUNCATED AT 400 WORDS)