Pacinian corpuscles in the human fetal foot: A study using 3D reconstruction and immunohistochemistry.

PURPOSE: Our group had recently described human hand Pacinian corpuscles (PCs): the hand PCs are not simply arranged along the digital palmar nerves but often exhibited specific morphologies known uncommonly. However, there is still no or few information about human foot PCs. MATERIALS AND METHODS: We observed transverse sections of all five toes including the interdigital area obtained from 12 feet of eight fetuses at 28-33 weeks (crown-rump length 230-290mm). Serial sections were prepared for 3D reconstructions and measurement. RESULTS: Foot PCs were characterized by (1) a dense distribution in the interdigital area in contrast to a few PCs in the distal tip of the all five toes; (2) abundant dorsal PCs including those in the nail bed and: (3) a long chain of PCs in the flexor tendon sheath of all five toes. Therefore, a distal dominance was not evident in the foot in contrast to the hand and, a tendon sheath contained much greater numbers of PCs than the hand. A tree-like or bouquet-like arrangement of PCs along a short perforating artery to the palmar digital skin was seen in the foot as we had described in the hand. The tree of foot PCs was sometimes seen laying transversely along the digital skin surface, not toward the skin. CONCLUSION: It is still unknown that, in utero, how the PCs distribution became different between the hand and foot: it might be determined genetically in a region-specific manner.

The development of human digital Meissner's and Pacinian corpuscles.

Meissner's and Pacinian corpuscles are cutaneous mechanoreceptors responsible for different modalities of touch. The development of these sensory formations in humans is poorly known, especially regarding the acquisition of the typical immunohistochemical profile related to their full functional maturity. Here we used a panel of antibodies (to specifically label the main corpuscular components: axon, Schwann-related cells and endoneurial-perineurial-related cells) to investigate the development of digital Meissner's and Pacinian corpuscles in a representative sample covering from 11 weeks of estimated gestational age (wega) to adulthood. Development of Pacinian corpuscles starts at 13 wega, and it is completed at 4 months of life, although their basic structure and immunohistochemical characteristics are reached at 36 wega. During development, around the axon, a complex network of S100 positive Schwann-related processes is progressively compacted to form the inner core, while the surrounding mesenchyme is organized and forms the outer core and the capsule. Meissner's corpuscles start to develop at 22 wega and complete their typical morphology and immunohistochemical profile at 8 months of life. In developing Meissner's corpuscles, the axons establish complex relationships with the epidermis and are progressively covered by Schwann-like cells until they complete the mature arrangement late in postnatal life. The present results demonstrate an asynchronous development of the Meissner's and Pacini's corpuscles and show that there is not a total correlation between morphological and immunohistochemical maturation. The correlation of the present results with touch-induced cortical activity in developing humans is discussed.

Pacinian Corpuscles in the Human Fetal Finger and Thumb: A Study Using 3D Reconstruction and Immunohistochemistry.

The detailed distribution of Pacinian corpuscles was evaluated by viewing the transverse sections of all fingers and thumbs, including the interdigital areas, from eight hands of five fetuses of gestational age 28-33 weeks (crown-rump length 230-290 mm). Among the 40 fingers and thumbs, serial sections were prepared for 3D reconstructions of nerve elements in the distal and middle phalangeal segments of three fifth fingers; in these three fingers, the distal segment contained 45-75 Pacinian corpuscles. These Pacinian corpuscles were 0.2-1.0 mm in length and 0.05-0.3 mm in thickness, oriented along the proximodistal axis and arranged along the palmar digital nerve branches. Other than beneath the digital skin, small corpuscles (<0.1 mm in thickness) were observed within the tendon sheath of the flexors in the middle or distal segment of five fetuses and in the nail beds of four fetuses. Clusters of 5-20 corpuscles formed bouquet- or tree-like arrangements along neurovascular bundles in the fingers, thumbs and interdigital areas. Because the space beneath the skin was thick and loose in the interdigital area, trees in the interdigital area were up to 2 mm long. Regardless of site, the central core of each corpuscle was positive for S100 protein, while the core and parts of the capillaries in the corpuscle were weakly positive for nestin. Because corpuscles in the tendon sheath and nail bed, as well as bouquet- and tree-like arrangements of corpuscles, have not been reported in adults, these morphologies are likely specific to fetuses. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 301:154-165, 2018. © 2017 Wiley Periodicals, Inc.

Tree of Vater-Pacinian corpuscles in the human finger and thumb: a comparison between the late fetal stage and old age.

Using histological sections of 12 hands from 12 human fetuses at 20-34 weeks of gestation (150-290 mm) and 14 fingers (index and small) from seven donated cadavers of elderly individuals (aged 78-95 years), we compared the features of Vater-Pacinian corpuscles between these two stages of life. Corpuscles with thin, tightly packed lamellae appeared to undergo a change to thick, loosely packed lamellae at 23-32 weeks. The typical fetal corpuscle had two parts: (1) a rod-like proximal part (0.2-0.6 mm in length) extending along the proximodistal axis of the finger, and (2) a distal end (0.1 mm) after acute bending of the proximal part. Corpuscles were associated with palmar digital nerves in the fingers, but were also present along the dorsal nerves in the thumb. A flower bouquet- or tree-like arrangement including 5-10 corpuscles extended to the dermis of the skin along a perforating artery. Serial sections of the thumb and fifth finger revealed approximately 80-180 corpuscles in the distal phalangeal segment. In elderly individuals, the corpuscles were distributed along the palmar digital nerve, but (1) their density was much lower than in fetuses and (2) a bouquet- or tree-like arrangement was rarely seen. In the distal segment, there were fewer than 40 adult corpuscles, being 0.2-0.5 mm thick and 1.0-2.5 mm long. Wavy or coiled corpuscles were evident. Because of the considerable differences in the distribution and number of corpuscles between the fetus and adult, they appear to undergo considerable depletion with age, especially along thin, superficial nerve branches.

c-Maf is required for the development of dorsal horn laminae III/IV neurons and mechanoreceptive DRG axon projections.

Establishment of proper connectivity between peripheral sensory neurons and their central targets is required for an animal to sense and respond to various external stimuli. Dorsal root ganglion (DRG) neurons convey sensory signals of different modalities via their axon projections to distinct laminae in the dorsal horn of the spinal cord. In this study, we found that c-Maf was expressed predominantly in the interneurons of laminae III/IV, which primarily receive inputs from mechanoreceptive DRG neurons. In the DRG, c-Maf⁺ neurons also coexpressed neurofilament-200, a marker for the medium- and large-diameter myelinated afferents that transmit non-noxious information. Furthermore, mouse embryos deficient in c-Maf displayed abnormal development of dorsal horn laminae III/IV neurons, as revealed by the marked reduction in the expression of several marker genes for these neurons, including those for transcription factors MafA and Rora, GABA(A) receptor subunit α5, and neuropeptide cholecystokinin. In addition, among the four major subpopulations of DRG neurons marked by expression of TrkA, TrkB, TrkC, and MafA/GFRα2/Ret, c-Maf was required selectively for the proper differentiation of MafA⁺/Ret⁺/GFRα2⁺ low-threshold mechanoreceptors (LTMs). Last, we found that the central and peripheral projections of mechanoreceptive DRG neurons were compromised in c-Maf deletion mice. Together, our results indicate that c-Maf is required for the proper development of MafA⁺/Ret⁺/GFRα2⁺ LTMs in the DRG, their afferent projections in the dorsal horn and Pacinian corpuscles, as well as neurons in laminae III/IV of the spinal cord.

Sensory nerve endings in the puborectalis and anal region of the fetus and newborn.

The study was carried out in seven fetuses (ovulation ages were 16, 18, 20, 22, 26, 28, and 31 weeks, respectively) and in five full-term newborn babies. The modified Bielschowsky method and Barker's block silver impregnation were used. It was found that the muscle spindle was arranged in the puborectalis and the external sphincter muscles from the 20th week onward; the tendon organ was located in association with the musculo-tendinous junction of the puborectalis from the 20th week onward; the Pacinian corpuscle lay in the plane of cleavage between the internal anal sphincter and the external anal sphincter from the 22nd week onward, and in the presacral space from the 28th week onward, and the later lagged behind the former in development; the globular endings lay in the presacral space from the 28th week onward; and the free nerve ending was distributed in the epithelium of the anal mucosa and the epidermis around the anus from the 31st week onward. These sensory nerve endings tend to mature gradually with increasing age. It was concluded that these endings may be responsible for the reflex of the external anal sphincter and the anal sensation.