Biology subjects

Koentges, G.

Publications and source records attributed to Koentges, G..

4 recordsLinked to original sources

bioRxiv2026

Dermal bone grows by cellular invasion and intercalary biomineralization

Dermal bone architecture bears great evolutionary significance for jawed vertebrates. Its thickness growth is believed to rely on matrix apposition by superficial osteoblasts. To test this hypothesis we employ genetic lineage mapping, conditional gene ablation, intravital matrix labelling and molecular 3D analysis at single cell resolution in vivo. We uncover an invasive mechanism incompatible with apposition. The pervasive arrangement of two layers sandwiching a third spongy layer develops from a molecularly defined bi-layer via a previously unknown developmental module: Outer layer osteoblasts form rosette-like assemblies around single invading cells. The latter bear unique molecular signatures and form de novo sheets inside the spongy layer, communicating with the layer below. The transcription factor Hand2 organizes this module by orchestrating rosette formation, their molecular heterogeneity, cellular invasion and spongy layer thickness growth. Surprisingly, invading osteoblasts secrete new biomineral matrix inside the older matrix, which keeps expanding. Such intercalary biomineralization provides new perspectives for bone biology and the evolution of endochondral ossification.

developmental biology↗

bioRxiv2026

A discrete Connexin26+ neural crest lineage emerges in mid-life and mediates enhanced central brainstem responses to elevated CO2 levels for deep breathing.

The precise control of breathing is fundamental to vertebrate survival. Increased PCO2 in blood and brain parenchyma causes an increase in both the frequency and volume of lung ventilation. We have previously demonstrated that CO2 directly binds to connexin26 (Cx26) hemichannels causing them to open and allow release ATP. We now document the role of Cx26 as a direct physiological CO2 sensor in vivo. Here we describe a unique Cx26+ neural crest cell lineage that populates the ventral brainstem in the vicinity of the PreBoetz nucleus/caudal CO2 chemosensory area during middle age and dies again in old age. Ablating Cx26 genetically specifically within this population of about 20 cells by two independent neural crest Cre-driver lines leads to a loss of local ATP release in the posterior chemosensory area as well as a 40% reduction in elevated tidal volume responses specifically in middle age, as measured by whole-body plethysmography. These in vivo effects change over a life-time: they directly mirror the arrival, wiring in middle age and later death of this cell population in old age. This is a first known example of a middle age change in cranial neural crest lineage composition and highlights the significant power of very few cells for global metabolism. Such lineage-dependent middle-age dynamics also impacts upon the evolution of eusociality: altricial naked pups of our common amniote/synapsid ancestors were heated by by the breath of their (middle-aged) carers, sensing elevated CO2 levels in hypercapnic burrows. Such mechanistic exaptation enabled small amniotes to sense and survive the lethal global CO2 spikes during the Permo-Triassic and other extinction events.

neuroscience↗

bioRxiv2026

Dermal bone remodelling by invasive osteoblasts evolved in stem gnathostomes

The evolutionary origin of the human face can be traced to the earliest vertebrates with a dermal skeleton in which canonical skeletal Issues and cell types arose. To elucidate its developmental evolution we performed genetic mosaic labelling, 3D single cell analysis and fluorescent matrix birthdating in vivo. We discover a common lineage origin of endothelial cells and osteoblasts and de novo vasculogenesis (not angiogenesis) as the dominant mechanism. Inside the spongy (cancellous) layer, invasive OPN+/RUNX2+ osteoblasts establish two orthogonal collagen sca[ff]olds, remodel them by directional secretion of matrix metalloproteinases and employ controllers of hydroxyapatite crystal resorption previously considered to be osteoclast- specific. Such intercalary biomineralization, comprising cellular sheet and volumetric biomineral expansion, renders all layers malleable even during postnatal stages. We trace this mechanism to bone ontogenies of the earliest skeletonizing vertebrates and resolve cell/Issue homologies controversial for almost two centuries. Our new model also has implications for bone matrix bioengineering and cancer osteomimicry that might replay some of these ontogenetic processes.

evolutionary biology↗

bioRxiv2024

Permissive and instructive Hox codes govern limb positioning

The positioning of limbs along the anterior-posterior axis varies widely across vertebrates. The mechanisms controlling this feature remain to be fully understood. For over 30 years, it has been speculated that Hox genes play a key role in this process but evidence supporting this hypothesis has been largely indirect. In this study, we employed loss- and gain-of-function Hox gene variants in chick embryos to address this issue. Using this approach, we found that Hox4/5 genes are necessary but insufficient for forelimb formation. Within the Hox4/5 expression domain, Hox6/7 genes are sufficient for reprogramming of neck lateral plate mesoderm to form an ectopic limb bud, thereby inducing forelimb formation anterior to the normal limb field. Our findings demonstrate that the forelimb program depends on the combinatorial actions of these Hox genes. We propose that during the evolutionary emergence of the neck, Hox4/5 provide permissive cues for forelimb formation throughout the neck region, while the final position of the forelimb is determined by the instructive cues of Hox6/7 in the lateral plate mesoderm. Impact statementElucidation of the Hox code defining forelimb positioning provides novel insights in lateral plate mesoderm patterning and the integration of vertebrate column structure and limb positioning.

developmental biology↗