Functional Anatomy: A Taxonomic Proposal

It is argued that medical science requires a classificatory system that (a) puts functions in the taxonomic center and (b) does justice ontologically to the difference between the processes which are the realizations of functions and the objects which are their bearers. We propose formulae for constructing such a system and describe some of its benefits. The arguments are general enough to be of interest to all the life sciences

Initial morphological symmetry breaking in the foregut and development of the omental bursa in human embryos

Bilaterally symmetrical primordia of visceral organs undergo asymmetrical morphogenesis leading to typical arrangement of visceral organs in the adult. Asymmetrical morphogenesis within the upper abdomen leads, among others, to the formation of the omental bursa dorsally to the rotated stomach. A widespread view of this process assumes kinking of thin mesenteries as a main mechanism. This view is based on a theory proposed already by Johannes Müller in 1830 and was repeatedly criticized, but some of the most plausible alternative views (initially proposed by Swaen in 1897 and Broman in 1904) still remain to be proven. Here, we analyzed serial histological sections of human embryos between stages 12 and 15 at high light microscopical resolution to reveal the succession of events giving rise to the development of the omental bursa and its relation to the emerging stomach asymmetry. Our analysis indicates that morphological symmetry breaking in the upper abdomen occurs within a wide mesenchymal plate called here mesenteric septum and is based on differential behavior of the coelomic epithelium which causes asymmetric paragastric recess formation and, importantly, precedes initial rotation of stomach. Our results thus provide the first histological evidence of breaking the symmetry of the early foregut anlage in the human embryo and pave the way for experimental studies of left-right symmetry breaking in the upper abdomen in experimental model organisms

Molecular left-right patterning after formin inhibition.

(A) Scheme of time course of chemical treatment and stages of LR analysis. (B, B’) Formin inhibitor SMIFH2 had no effect on nodal1 expression patterns in the embryos treated during cleavage (N = 3) and reduced the proportion of left-sided nodal1 expression in the embryos treated during gastrulation and neurulation (N = 6, p = 0,00000313 for 10μM SMIFH2). (B) Summary of experimental data. (B’) Representative images of formin-modulated stage 28 tailbud embryos displaying left-sided and abnormal (right, absent and bilateral) expression of nodal1, ventral view. (C, C’) Formin inhibitor SMIFH2 had no effect on pitx2 expression patterns in the embryos treated during cleavage (N = 4) and reduced the proportion of left-sided pitx2 expression in the embryos treated during gastrulation and neurulation (N = 7, p = 0,0005445 for 10μM SMIFH2). (C) Summary of experimental data. (C’) Representative images of formin-modulated stage 28 tailbud embryos displaying left-sided and abnormal (right, absent and bilateral) expression of pitx2, ventral view. A, anterior; L, left; P, posterior; R, right. ***, p-value<0.001 compared with the DMSO control, two-proportions z-test with Bonferroni correction; N, number of experiments. Numbers at the base of columns represent number of analyzed embryos.</p

Representative histological sections through GRP of embryos at stage 18 treated with 10 μM SMIFH2 at stages 10–18, demonstrating position of <i>nodal1</i> and <i>dand5</i> expressing cells.

Arrows indicate areas of superficial nodal1 and dand5-positilklllve cells. (JPG)</p

Formin inhibition at gastrula and neurula stages results in morphology defects of left-right organizer at stage 18.

(A) Representative scanning electron microscopy images of GRP after exposure to various concentrations of formin inhibitor. (B) Representative histological sections through the GRP after exposure to various concentrations of formin inhibitor. Blue color indicates ectoderm, red–notochord and hypochord, violet–somitic mesoderm, yellow–endoderm. (C) Cilia polarization, cilia length and percentage of ciliated cells (ciliation rate) in embryos treated with DMSO and SMIFH2 (5 μM and 10 μM). Measurements were performed in notochordal GRP of 11, 14 and 9 embryos respectively (number of analysed cells = 303, 453 and 234 respectively). The apparent decrease of number of ciliated cells is non-significant (p-value = 0,295 for 10 μM, t-test with Bonferroni correction).</p

Visceral organ situs after formin inhibition.

(A) Representative images of formin-modulated stage 46 tadpoles displaying normal organ situs (ss), situs inversion (si), or heterotaxia (ht), as determined by the direction of heart looping (outlined by dashed red line) and gut coiling (outlined by dashed violet line), ventral view. (B) Formin inhibitor SMIFH2 had no effect on organ situs in the tadpoles treated during cleavage (N = 5) and reduced the proportion of tadpoles with normal organ laterality after treatment with 10 μM SMIFH2 during gastrulation and neurulation (N = 5). a, anterior; ht, heterotaxia; l, left; p, posterior; r, right; si, situs inversus; ss, situs solitus. Cyan arrows indicate heart ventricle, yellow arrows indicate truncus arteriosus. ***, p-value = 0,00006552 compared with the DMSO control, two-proportions z-test with Bonferroni correction; N, number of experiments. Numbers at the base of columns represent number of analyzed embryos.</p

Le Peuple : organe quotidien du syndicalisme

09 mai 19331933/05/09 (A13,N4496)-1933/05/09

Formin inhibition at gastrula and neurula stages results in abnormal molecular patterning of GRP.

(A-B’) Representative images of molecular patterning in the GRP. Dorsal explants of stage 18 neurula embryos after control treatment (A,B) and SMIFH2 administration (A’,B’) at stages 10–18. In situ hybridisation was performed with probes specific for sox17 (A,A’) and tekt2 (B,B’). (C and C’) Representative images of nodal1 expression pattern in the GRP. Dorsal explants of stage 18 neurula embryos after control or SMIFH2 treatment at stages 10–18. (D and D’) Histological sections through GRP demonstrate the position of nodal1-positive cells in the prospective somitic mesoderm. Arrows indicate areas of superficial nodal1-positive cells.</p

S2 Fig -

Expression of endodermal marker sox17 and tekt2, a marker of cells forming motile cilia in GRP of embryos treated with DMSO and SMIFH2 from stage 10, fixated at late gastrulation (A and B) and at stage 18 (C and D). (JPG)</p

Formin inhibition at cleavage stages has no effect on morphology and molecular anatomy of GRP in embryos treated with DMSO and 10 μM SMIFH2.

(A) Representative scanning electron microscopy images of GRP. Dorsal explants of stage 18 neurula embryos after formin inhibition at stages 2–6.5. Red color indicates notochord and hypochord, violet–somitic mesoderm, yellow–endoderm. (B-D) Representative images of molecular patterning in the GRP. Dorsal explants of stage 18 neurula embryos after formin inhibition at stages 2–6.5. In situ hybridisation was performed with probes specific for nodal1 (B), sox17 (C) and tekt2 (D). (JPG)</p