One of the hallmarks of developmental processes is that cells must communicate with each other to develop proper spatial arrangements of tissues and cellular sub types. This communication occurs through cell signaling mechanisms. These cell-cell communication systems are commonly composed of a cell surface receptor and the molecule, called a ligand, that binds to it. On ligand binding, receptors transmit their signals through intra cellular signaling pathways. One of the common ligand receptor pairs is the fibroblast growth factors and their receptors. There are 23 recognized members of the fibroblast growth factor gene family in the human, and many of them are important in development. The fibro blast growth factors serve as ligands for tyrosine kinase receptors. Abnormalities in fibroblast growth factor receptors cause diseases such as achondroplasia and certain syndromes that involve abnormalities of craniofacial development, referred to as craniosynostoses because they demonstrate premature fusion of cranial sutures in the skull.

One of the best examples of a developmental morphogen is hedgehog, originally discovered in Drosophila and named for its ability to alter the orientation of epidermal bristles. Diffusion of the hedgehog protein creates a gradient in which different concentrations of the protein cause surrounding cells to assume different fates. In humans, three genes closely related to Drosophila hedgehog also encode developmental morphogens; one example is the gene sonic hedgehog (SHH). Although the specific programs controlled by hedgehog in Drosophila are very different from those controlled by its mammalian counterparts, the underlying themes and molecular mechanisms are similar. For example, secretion of the SHH protein by the notochord and the floor plate of the developing neural tube generates a gradient that induces and organizes the different types of cells and tissues in the developing brain and spinal cord (Fig. 1A). SHH is also produced by a small group of cells in the limb bud known as the zone of polarizing activity, which is responsible for establishing the posterior side of the developing limb bud and the asymmetric pattern of digits within individual limbs (see Fig. 1B).

Fig1. (A) Transverse section of the developing neural tube. Sonic hedgehog protein released from the notochord diffuses upward to the ventral portion of the developing neural tube (brown); high concentrations immediately above the notochord induce the floor plate, whereas lower concentrations more laterally induce motor neurons. Ectoderm above (dorsal to) the neural tube releases bone morphogenetic proteins that help induce neural crest development at the dorsal edge of the closing neural tube (dark purple). (B) Morphogenetic action of the sonic hedgehog (SHH) protein during limb bud formation. SHH is released from the zone of polarizing activity (labeled polarizing region in B) in the posterior limb bud to produce a gradient (shown with its highest levels as 4, declining to 2). Mutations or transplantation experiments that create an ectopic polarizing region in the anterior limb bud cause a duplication of posterior limb elements. (A, From Lumsden A, Graham A: Neural patterning: A forward role for hedgehog, Curr Biol 5:1347–1350, 1995. Copyright 1995, Elsevier Science; B, from Wolpert L, Beddington R, Brockes J, et al: Principles of development, New York, 1998, Oxford University Press.)

Variants that inactivate the SHH gene in humans cause birth defects that may be inherited as autosomal dominant traits, which demonstrates that a 50% reduction in gene expression is sufficient to produce an abnormal phenotype, presumably by altering the magnitude of the hedgehog protein gradient. Affected individuals usually exhibit holoprosencephaly (failure of the mid face and forebrain to develop), leading to absence of forebrain structures and hypotelorism (closely spaced eyes), and they have cleft lip and palate. On occasion, however, the clinical findings are mild or subtle such as, for example, a single central incisor or partial absence of the corpus callosum . Because variable expressivity has been observed in members of the same family, it cannot be due to different variants and instead must reflect the action of modifier genes at other loci, chance, environment, or some combination of all three.

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اخبار العتبة العباسية المقدسة

شعبة الحرم الشريف تستعد لاستقبال زائري النصف من شهر شعبان

العتبة العباسية المقدسة تنشر لافتات الفرح بمناسبة ذكرى ولادة الإمام المهدي (عجّل الله فرجه)

العتبة العباسية المقدسة تفتتح التسجيل لتأدية الزيارة بالنيابة في ليلة النصف من شعبان

قسم المقام يعلن جاهزيّته لاستقبال زائري النصف من شعبان

المزيد

الآخبار الصحية

الصحة العالمية تكشف حقيقة انتشار فيروس نيباه خارج الهند

متى يصبح محيط الخصر "مؤشر خطر"؟

دراسة تكشف دور "العوامل الوراثية" في تحديد عمر الإنسان

رائحة كريهة في الجسم.. "علامة خفية" أخطر مما تتصور

المزيد

الآخبار التكنلوجية

مايكروسوفت تكشف عن الجيل الثاني من شرائحها للذكاء الاصطناعي

خرافة "ثمانية أكواب يوميا".. كم من الماء يحتاج جسمك فعليا؟

هل توجد حياة خارج كوكبنا؟.. اكتشاف جديد يثير اهتمام العلماء

اكتشاف الخلايا المسؤولة عن فقدان ذاكرة الطفولة

المزيد

مواضيع ذات صلة

Thrombopoietin Signaling

Mechanisms of Endomitosis in Megakaryocytes

Megakaryocytopoiesis

Ontogeny of Erythropoiesis

Cellular Dynamics in Erythropoiesis: Steady State and Stress Erythropoiesis

Erythropoiesis and Iron Regulation

Hematopoietic Microenvironment

Intrinsic Control of Erythropoiesis:Erythropoietin

Nuclear Organization

Unfolded Protein Response

Autophagy

Nonapoptotic forms of cell death